Tolerogenic dendritic cells; Regulation; Immunity; Regulatory T cells
Abstract :
[en] Immune responses against pathogens require fine regulation in order to avoid excessive inflammation, which could be harmful to the host. Moreover, the immune system must be tolerant to non-pathogenic antigens in order to prevent allergy, autoimmunity and transplant rejection. There is accumulating evidence that interactions between dendritic cells (DC) and regulatory T (Treg) cells play a crucial role in the balance between immune response and tolerance. Communications between these cells are complex, bi-directional and mediated by soluble or cell surface molecules. The maturation status of DC, which may be influenced by different microenvironmental factors, is considered as an important checkpoint for the induction of peripheral tolerance through modifications of the activation status of T cells. Moreover, several lines of experimental evidence suggest that different subsets or the functional status of DC are also involved in the promotion of Treg cell differentiation. A better knowledge of the regulatory mechanisms of the immune response induced or inhibited by DC via their interactions with Treg cells could be relevant for the development of new immunotherapeutic approaches.
Research center :
CRCE
Disciplines :
Immunology & infectious disease
Author, co-author :
Hubert, Pascale ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Jacobs, Nathalie ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Caberg, Jean-Hubert ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Boniver, Jacques ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Delvenne, Philippe ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Language :
English
Title :
The cross-talk between dendritic and regulatory T cells: good or evil?
Publication date :
October 2007
Journal title :
Journal of Leukocyte Biology
ISSN :
0741-5400
Publisher :
Wiley Liss, Inc., New York, United States - New York
De Jong, E. C., Smits, H. H., Kapsenberg, M. L. (2005) Dendritic cell-mediated T cell polarization. Springer Semin. Immunopathol. 26, 289-307.
Yamazaki, S., Patel, M., Harper, A., Bonito, A., Fukuyama, H., Pack, M., Tarbell, K. V., Talmor, M., Ravetch, J. V., Inaba, K., Steinman, R. M. (2006) Effective expansion of alloantigen-specific Foxp3+ CD25+ CD4+ regulatory T cells by dendritic cells during the mixed leukocyte reaction. Proc. Natl. Acad. Sci. USA 103, 2758-2763.
Tarbell, K. V., Yamazaki, S., Steinman, R. M. (2006) The interactions of dendritic cells with antigen-specific, regulatory T cells that suppress autoimmunity. Semin. Immunol. 18, 93-102.
Kubach, J., Becker, C., Schmitt, E., Steinbrink, K., Huter, E., Tuettenberg, A., Jonuleit, H. (2005) Dendritic cells: sentinels of immunity and tolerance. Int. J. Hematol. 81, 197-203.
Tan, J. K., O'Neill, H. C. (2005) Maturation requirements for dendritic cells in T cell stimulation leading to tolerance versus immunity. J. Leukoc. Biol. 78, 319-324.
Jonuleit, H., Schmitt, E., Schuler, G., Knop, J., Enk, A. H. (2000) Induction of interleukin 10-producing, nonproliferating CD4(+) T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells. J. Exp. Med. 192, 1213-1222.
Mahnke, K., Qian, Y., Knop, J., Enk, A. H. (2003) Induction of CD4+/CD25+ regulatory T cells by targeting of antigens to immature dendritic cells. Blood 101, 4862-4869.
Bonifaz, L., Bonnyay, D., Mahnke, K., Rivera, M., Nussenzweig, M. C., Steinman, R. M. (2002) Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8+ T cell tolerance. J. Exp. Med. 196, 1627-1638.
Hawiger, D., Inaba, K., Dorsett, Y., Guo, M., Mahnke, K., Rivera, M., Ravetch, J. V., Steinman, R. M., Nussenzweig, M. C. (2001) Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo. J. Exp. Med. 194, 769-779.
Dhodapkar, M. V., Steinman, R. M. (2002) Antigen-bearing immature dendritic cells induce peptide-specific CD8(+) regulatory T cells in vivo in humans. Blood 100, 174-177.
Suss, G., Shortman, K. (1996) A subclass of dendritic cells kills CD4 T cells via Fas/Fas-ligand-induced apoptosis. J. Exp. Med. 183, 1789-1796.
Belz, G. T., Behrens, G. M., Smith, C. M., Miller, J. F., Jones, C., Lejon, K., Fathman, C. G., Mueller, S. N., Shortman, K., Carbone, F. R., Heath, W. R. (2002) The CD8α(+) dendritic cell is responsible for inducing peripheral self-tolerance to tissue-associated antigens. J. Exp. Med. 196, 1099-1104.
Kronin, V., Wu, L., Gong, S., Nussenzweig, M. C., Shortman, K. (2000) DEC-205 as a marker of dendritic cells with regulatory effects on CD8 T cell responses. Int. Immunol. 12, 731-735.
Kronin, V., Fitzmaurice, C. J., Caminschi, I., Shortman, K., Jackson, D. C., Brown, L. E. (2001) Differential effect of CD8(+) and CD8(-) dendritic cells in the stimulation of secondary CD4(+) T cells. Int. Immunol. 13, 465-473.
Steinman, R. M., Turley, S., Mellman, I., Inaba, K. (2000) The induction of tolerance by dendritic cells that have captured apoptotic cells. J. Exp. Med. 191, 411-416.
Stuart, L. M., Lucas, M., Simpson, C., Lamb, J., Savill, J., Lacy-Hulbert, A. (2002) Inhibitory effects of apoptotic cell ingestion upon endotoxin-driven myeloid dendritic cell maturation. J. Immunol. 168, 1627-1635.
Kim, S., Elkon, K. B., Ma, X. (2004) Transcriptional suppression of interleukin-12 gene expression following phagocytosis of apoptotic cells. Immunity 21, 643-653.
Wallet, M. A., Sen, P., Tisch, R. (2005) Immunoregulation of dendritic cells. Clin. Med. Res. 3, 166-175.
Penna, G., Adorini, L. (2000) 1 α,25-dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation. J. Immunol. 164, 2405-2411.
Lagaraine, C., Lebranchu, Y. (2003) Effects of immunosuppressive drugs on dendritic cells and tolerance induction. Transplantation 75, 37S-42S.
Steinbrink, K., Wolfl, M., Jonuleit, H., Knop, J., Enk, A. H. (1997) Induction of tolerance by IL-10-treated dendritic cells. J. Immunol. 159, 4772-4780.
Schlichting, C. L., Schareck, W. D., Nickel, T., Weis, M. (2005) Dendritic cells as pharmacological targets for the generation of regulatory immunosuppressive effectors. New implications for allo-transplantation. Curr. Med. Chem. 12, 1921-1930.
McBride, J. M., Jung, T., de Vries, J. E., Aversa, G. (2002) IL-10 alters DC function via modulation of cell surface molecules resulting in impaired T-cell responses. Cell. Immunol. 215, 162-172.
Steinbrink, K., Graulich, E., Kubsch, S., Knop, J., Enk, A. H. (2002) CD4(+) and CD8(+) anergic T cells induced by interleukin-10-treated human dendritic cells display antigen-specific suppressor activity. Blood 99, 2468-2476.
Sato, K., Yamashita, N., Baba, M., Matsuyama, T. (2003) Modified myeloid dendritic cells act as regulatory dendritic cells to induce anergic and regulatory T cells. Blood 101, 3581-3589.
Enk, A. H., Jonuleit, H., Saloga, J., Knop, J. (1997) Dendritic cells as mediators of tumor-induced tolerance in metastatic melanoma. Int. J. Cancer 73, 309-316.
Cortesini, R., LeMaoult, J., Ciubotariu, R., Cortesini, N. S. (2001) CD8+CD28- T suppressor cells and the induction of antigen-specific, antigen-presenting cell-mediated suppression of Th reactivity. Immunol. Rev. 182, 201-206.
Chang, C. C., Ciubotariu, R., Manavalan, J. S., Yuan, J., Colovai, A. I., Piazza, F., Lederman, S., Colonna, M., Cortesini, R., Dalla-Favera, R., Suciu-Foca, N. (2002) Tolerization of dendritic cells by T(S) cells: the crucial role of inhibitory receptors ILT3 and ILT4. Nat. Immunol. 3, 237-243.
Suciu-Foca, N., Manavalan, J. S., Cortesini, R. (2003) Generation and function of antigen-specific suppressor and regulatory T cells. Transpl. Immunol. 11, 235-244.
Lutz, M. B., Schuler, G. (2002) Immature, semi-mature and fully mature dendritic cells: which signals induce tolerance or immunity? Trends Immunol. 23, 445-449.
Voigtlander, C., Rossner, S., Cierpka, E., Theiner, G., Wiethe, C., Menges, M., Schuler, G., Lutz, M. B. (2006) Dendritic cells matured with TNF can be further activated in vitro and after subcutaneous injection in vivo which converts their tolerogenicity into immunogenicity. J. Immunother. 29, 407-415.
Menges, M., Rossner, S., Voigtlander, C., Schindler, H., Kukutsch, N. A., Bogdan, C., Erb, K., Schuler, G., Lutz, M. B. (2002) Repetitive injections of dendritic cells matured with tumor necrosis factor α induce antigen-specific protection of mice from autoimmunity. J. Exp. Med. 195, 15-21.
Mahnke, K., Enk, A. H. (2005) Dendritic cells: key cells for the induction of regulatory T cells? Curr. Top. Microbiol. Immunol. 293, 133-150.
Kuwana, M. (2002) Induction of anergic and regulatory T cells by plasmacytoid dendritic cells and other dendritic cell subsets. Hum. Immunol. 63, 1156-1163.
Ito, T., Inaba, M., Inaba, K., Toki, J., Sogo, S., Iguchi, T., Adachi, Y., Yamaguchi, K., Amakawa, R., Valladeau, J., Saeland, S., Fukuhara, S., Ikehara, S. (1999) A CD1a+/CD11c+ subset of human blood dendritic cells is a direct precursor of Langerhans cells. J. Immunol. 163, 1409-1419.
Gilliet, M., Liu, Y. J. (2002) Generation of human CD8 T regulatory cells by CD40 ligand-activated plasmacytoid dendritic cells. J. Exp. Med. 195, 695-704.
Ochando, J. C., Homma, C., Yang, Y., Hidalgo, A., Garin, A., Tacke, F., Angeli, V., Li, Y., Boros, P., Ding, Y., Jessberger, R., Trinchieri, G., Lira, S. A., Randolph, G. J., Bromberg, J. S. (2006) Alloantigen-presenting plasmacytoid dendritic cells mediate tolerance to vascularized grafts. Nat. Immunol. 7, 652-662.
Wei, S., Kryczek, I., Zou, L., Daniel, B., Cheng, P., Mottram, P., Curiel, T., Lange, A., Zou, W. (2005) Plasmacytoid dendritic cells induce CD8+ regulatory T cells in human ovarian carcinoma. Cancer Res. 65, 5020-5026.
Liu, Y. J. (2006) A unified theory of central tolerance in the thymus. Trends Immunol. 27, 215-221.
Watanabe, N., Wang, Y. H., Lee, H. K., Ito, T., Wang, Y. H., Cao, W., Liu, Y. J. (2005) Hassall's corpuscles instruct dendritic cells to induce CD4+CD25+ regulatory T cells in human thymus. Nature 436, 1181-1185.
Yamazaki, S., Iyoda, T., Tarbell, K., Olson, K., Velinzon, K., Inaba, K., Steinman, R. M. (2003) Direct expansion of functional CD25+ CD4+ regulatory T cells by antigen-processing dendritic cells. J. Exp. Med. 198, 235-247.
Tarbell, K. V., Yamazaki, S., Olson, K., Toy, P., Steinman, R. M. (2004) CD25+ CD4+ T cells, expanded with dendritic cells presenting a single autoantigenic peptide, suppress autoimmune diabetes. J. Exp. Med. 199, 1467-1477.
Verhasselt, V., Vosters, O., Beuneu, C., Nicaise, C., Stordeur, P., Goldman, M. (2004) Induction of FOXP3-expressing regulatory CD4pos T cells by human mature autologous dendritic cells. Eur. J. Immunol. 34, 762-772.
Rutella, S., Lemoli, R. M. (2004) Regulatory T cells and tolerogenic dendritic cells: from basic biology to clinical applications. Immunol. Lett. 94, 11-26.
Schreiner, B., Mitsdoerffer, M., Kieseier, B. C., Chen, L., Hartung, H. P., Weller, M., Wiendl, H. (2004) Interferon-β enhances monocyte and dendritic cell expression of B7-H1 (PD-L1), a strong inhibitor of autologous T-cell activation: relevance for the immune modulatory effect in multiple sclerosis. J. Neuroimmunol. 155, 172-182.
Suciu-Foca, N., Manavalan, J. S., Scotto, L., Kim-Schulze, S., Galluzzo, S., Naiyer, A. J., Fan, J., Vlad, G., Cortesini, R. (2005) Molecular characterization of allospecific T suppressor and tolerogenic dendritic cells: review. Int. Immunopharmacol. 5, 7-11.
Vlad, G., Piazza, F., Colovai, A., Cortesini, R., Della Pietra, F., Suciu-Foca, N., Manavalan, J. S. (2003) Interleukin-10 induces the upregulation of the inhibitory receptor ILT4 in monocytes from HIV positive individuals. Hum. Immunol. 64, 483-489.
Manavalan, J. S., Rossi, P. C., Vlad, G., Piazza, F., Yarilina, A., Cortesini, R., Mancini, D., Suciu-Foca, N. (2003) High expression of ILT3 and ILT4 is a general feature of tolerogenic dendritic cells. Transpl. Immunol. 11, 245-258.
Munn, D. H., Sharma, M. D., Baban, B., Harding, H. P., Zhang, Y., Ron, D., Mellor, A. L. (2005) GCN2 kinase in T cells mediates proliferative arrest and anergy induction in response to indoleamine 2,3-dioxygenase. Immunity 22, 633-642.
Munn, D. H., Sharma, M. D., Hou, D., Baban, B., Lee, J. R., Antonia, S. J., Messina, J. L., Chandler, P., Koni, P. A., Mellor, A. L. (2004) Expression of indoleamine 2,3-dioxygenase by plasmacytoid dendritic cells in tumor-draining lymph nodes. J. Clin. Invest. 114, 280-290.
Mellor, A. L., Chandler, P., Baban, B., Hansen, A. M., Marshall, B., Pihkala, J., Waldmann, H., Cobbold, S., Adams, E., Munn, D. H. (2004) Specific subsets of murine dendritic cells acquire potent T cell regulatory functions following CTLA4-mediated induction of indoleamine 2,3 dioxygenase. Int. Immunol. 16, 1391-1401.
Khoury, S. J., Sayegh, M. H. (2004) The roles of the new negative T cell costimulatory pathways in regulating autoimmunity. Immunity 20, 529-538.
McHugh, R. S., Whitters, M. J., Piccirillo, C. A., Young, D. A., Shevach, E. M., Collins, M., Byrne, M. C. (2002) CD4(+)CD25(+) immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoid- induced TNF receptor. Immunity 16, 311-323.
Stephens, G. L., McHugh, R. S., Whitters, M. J., Young, D. A., Luxenberg, D., Carreno, B. M., Collins, M., Shevach, E. M. (2004) Engagement of glucocorticoid-induced TNFR family-related receptor on effector T cells by its ligand mediates resistance to suppression by CD4+CD25+ T cells. J. Immunol. 173, 5008-5020.
Fontenot, J. D., Rasmussen, J. P., Williams, L. M., Dooley, J. L., Farr, A. G., Rudensky, A. Y. (2005) Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity 22, 329-341.
Liu, W., Putnam, A. L., Xu-Yu, Z., Szot, G. L., Lee, M. R., Zhu, S., Gottlieb, P. A., Kapranov, P., Gingeras, T. R., de St Groth, B. F., Clayberger, C., Soper, D. M., Ziegler, S. F., Bluestone, J. A. (2006) CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells. J. Exp. Med. 203, 1701-1711.
Von Boehmer, H. (2005) Mechanisms of suppression by suppressor T cells. Nat. Immunol. 6, 338-344.
Esparza, E. M., Arch, R. H. (2006) Signaling triggered by glucocorticoid-induced tumor necrosis factor receptor family-related gene: regulation at the interface between regulatory T cells and immune effector cells. Front. Biosci. 11, 1448-1465.
Shevach, E. M. (2006) From vanilla to 28 flavors: multiple varieties of T regulatory cells. Immunity 25, 195-201.
Shevach, E. M., DiPaolo, R. A., Andersson, J., Zhao, D. M., Stephens, G. L., Thornton, A. M. (2006) The lifestyle of naturally occurring CD4+ CD25+ Foxp3+ regulatory T cells. Immunol. Rev. 212, 60-73.
Wing, K., Fehervari, Z., Sakaguchi, S. (2006) Emerging possibilities in the development and function of regulatory T cells. Int. Immunol. 18, 991-1000.
Sakaguchi, S., Sakaguchi, N., Asano, M., Itoh, M., Toda, M. (1995) Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor α-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J. Immunol. 155, 1151-1164.
Groux, H., O'Garra, A., Bigler, M., Rouleau, M., Antonenko, S., de Vries, J. E., Roncarolo, M. G. (1997) A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 389, 737-742.
Weiner, H. L. (2001) The mucosal milieu creates tolerogenic dendritic cells and T(R)1 and T(H)3 regulatory cells. Nat. Immunol. 2, 671-672.
Cosmi, L., Liotta, F., Lazzeri, E., Francalanci, M., Angeli, R., Mazzinghi, B., Santarlasci, V., Manetti, R., Vanini, V., Romagnani, P., Maggi, E., Romagnani, S., Annunziato, F. (2003) Human CD8+CD25+ thymocytes share phenotypic and functional features with CD4+CD25+ regulatory thymocytes. Blood 102, 4107-4114.
Endharti, A. T., Rifa'I., M., Shi, Z., Fukuoka, Y., Nakahara, Y., Kawamoto, Y., Takeda, K., Isobe, K., Suzuki, H. (2005) Cutting edge: CD8+CD122+ regulatory T cells produce IL-10 to suppress IFN-γ production and proliferation of CD8+ T cells. J. Immunol. 175, 7093-7097.
Graca, L., Silva-Santos, B., Coutinho, A. (2006) The blind-spot of regulatory T cells. Eur. J. Immunol. 36, 802-805.
Suffia, I. J., Reckling, S. K., Piccirillo, C. A., Goldszmid, R. S., Belkaid, Y. (2006) Infected site-restricted Foxp3+ natural regulatory T cells are specific for microbial antigens. J. Exp. Med. 203, 777-788.
Vigouroux, S., Yvon, E., Biagi, E., Brenner, M. K. (2004) Antigen-induced regulatory T cells. Blood 104, 26-33.
Taams, L. S., Akbar, A. N. (2005) Peripheral generation and function of CD4+CD25+ regulatory T cells. Curr. Top. Microbiol. Immunol. 293, 115-131.
Taylor, A., Verhagen, J., Blaser, K., Akdis, M., Akdis, C. A. (2006) Mechanisms of immune suppression by interleukin-10 and transforming growth factor-β: the role of T regulatory cells. Immunology 117, 433-442.
Buckner, J. H., Ziegler, S. F. (2004) Regulating the immune system: the induction of regulatory T cells in the periphery. Arthritis Res. Ther. 6, 215-222.
Jonuleit, H., Schmitt, E. (2003) The regulatory T cell family: distinct subsets and their interrelations. J. Immunol. 171, 6323-6327.
Berlin, C., Bargatze, R. F., Campbell, J. J., von Andrian, U. H., Szabo, M. C., Hasslen, S. R., Nelson, R. D., Berg, E. L., Erlandsen, S. L., Butcher, E. C. (1995) α 4 integrins mediate lymphocyte attachment and rolling under physiologic flow. Cell 80, 413-422.
Chattopadhyay, S., Chakraborty, N. G., Mukherji, B. (2005) Regulatory T cells and tumor immunity. Cancer Immunol. Immunother. 54, 1153-1161.
Manavalan, J. S., Kim-Schulze, S., Scotto, L., Naiyer, A. J., Vlad, G., Colombo, P. C., Marboe, C., Mancini, D., Cortesini, R., Suciu-Foca, N. (2004) Alloantigen specific CD8+CD28- FOXP3+ T suppressor cells induce ILT3+ ILT4+ tolerogenic endothelial cells, inhibiting alloreactivity. Int. Immunol. 16, 1055-1068.
Hu, D., Ikizawa, K., Lu, L., Sanchirico, M. E., Shinohara, M. L., Cantor, H. (2004) Analysis of regulatory CD8 T cells in Qa-1-deficient mice. Nat. Immunol. 5, 516-523.
Vlad, G., Cortesini, R., Suciu-Foca, N. (2005) License to heal: bidirectional interaction of antigen-specific regulatory T cells and tolerogenic APC. J. Immunol. 174, 5907-5914.
Cantor, H. (2004) Reviving suppression? Nat. Immunol. 5, 347-349.
Ghiringhelli, F., Puig, P. E., Roux, S., Parcellier, A., Schmitt, E., Solary, E., Kroemer, G., Martin, F., Chauffert, B., Zitvogel, L. (2005) Tumor cells convert immature myeloid dendritic cells into TGF-β-secreting cells inducing CD4+CD25+ regulatory T cell proliferation. J. Exp. Med. 202, 919-929.
Kretschmer, K., Apostolou, I., Hawiger, D., Khazaie, K., Nussenzweig, M. C., von Boehmer, H. (2005) Inducing and expanding regulatory T cell populations by foreign antigen. Nat. Immunol. 6, 1219-1227.
Von Herrath, M. G., Harrison, L. C. (2003) Antigen-induced regulatory T cells in autoimmunity. Nat. Rev. Immunol. 3, 223-232.
Shevach, E. M. (2002) CD4+ CD25+ suppressor T cells: more questions than answers. Nat. Rev. Immunol. 2, 389-400.
Sakaguchi, S. (2005) Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat. Immunol. 6, 345-352.
Wang, H. Y., Lee, D. A., Peng, G., Guo, Z., Li, Y., Kiniwa, Y., Shevach, E. M., Wang, R. F. (2004) Tumor-specific human CD4+ regulatory T cells and their ligands: implications for immunotherapy. Immunity 20, 107-118.
Grossman, W. J., Verbsky, J. W., Barchet, W., Colonna, M., Atkinson, J. P., Ley, T. J. (2004) Human T regulatory cells can use the perforin pathway to cause autologous target cell death. Immunity 21, 589-601.
Gondek, D. C., Lu, L. F., Quezada, S. A., Sakaguchi, S., Noelle, R. J. (2005) Cutting edge: contact-mediated suppression by CD4+CD25+ regulatory cells involves a granzyme B-dependent, perforin-independent mechanism. J. Immunol. 174, 1783-1786.
De la Rosa, M., Rutz, S., Dorninger, H., Scheffold, A. (2004) Interleukin-2 is essential for CD4+CD25+ regulatory T cell function. Eur. J. Immunol. 34, 2480-2488.
Cobbold, S. P., Nolan, K. F., Graca, L., Castejon, R., Le Moine, A., Frewin, M., Humm, S., Adams, E., Thompson, S., Zelenika, D., Paterson, A., Yates, S., Fairchild, P. J., Waldmann, H. (2003) Regulatory T cells and dendritic cells in transplantation tolerance: molecular markers and mechanisms. Immunol. Rev. 196, 109-124.
Kryczek, I., Wei, S., Zou, L., Zhu, G., Mottram, P., Xu, H., Chen, L., Zou, W. (2006) Cutting edge: induction of B7-H4 on APCs through IL-10: novel suppressive mode for regulatory T cells. J. Immunol. 177, 40-44.
Cederbom, L., Hall, H., Ivars, F. (2000) CD4+CD25+ regulatory T cells down-regulate co-stimulatory molecules on antigen-presenting cells. Eur. J. Immunol. 30, 1538-1543.
Oderup, C., Cederbom, L., Makowska, A., Cilio, C. M., Ivars, F. (2006) Cytotoxic T lymphocyte antigen-4-dependent down-modulation of costimulatory molecules on dendritic cells in CD4+ CD25+ regulatory T-cell-mediated suppression. Immunology 118, 240-249.
Larmonier, N., Marron, M., Zeng, Y., Cantrell, J., Romanoski, A., Sepassi, M., Thompson, S., Chen, X., Andreansky, S., Katsanis, E. (2007) Tumor-derived CD4(+)CD25(+) regulatory T cell suppression of dendritic cell function involves TGF-β and IL-10. Cancer Immunol. Immunother. 56, 48-59.
Sato, K., Tateishi, S., Kubo, K., Mimura, T., Yamamoto, K., Kanda, H. (2005) Downregulation of IL-12 and a novel negative feedback system mediated by CD25+CD4+ T cells. Biochem. Biophys. Res. Commun. 330, 226-232.
Mellor, A. L., Munn, D. H. (2004) IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nat. Rev. Immunol. 4, 762-774.
Fallarino, F., Grohmann, U., Hwang, K. W., Orabona, C., Vacca, C., Bianchi, R., Belladonna, M. L., Fioretti, M. C., Alegre, M. L., Puccetti, P. (2003) Modulation of tryptophan catabolism by regulatory T cells. Nat. Immunol. 4, 1206-1212.
Sica, G. L., Choi, I. H., Zhu, G., Tamada, K., Wang, S. D., Tamura, H., Chapoval, A. I., Flies, D. B., Bajorath, J., Chen, L. (2003) B7-H4, a molecule of the B7 family, negatively regulates T cell immunity. Immunity 18, 849-861.
Gershon, R. K., Kondo, K. (1971) Infectious immunological tolerance. Immunology 21, 903-914.
Jonuleit, H., Schmitt, E., Kakirman, H., Stassen, M., Knop, J., Enk, A. H. (2002) Infectious tolerance: human CD25(+) regulatory T cells convey suppressor activity to conventional CD4(+) T helper cells. J. Exp. Med. 196, 255-260.
Ghiringhelli, F., Menard, C., Terme, M., Flament, C., Taieb, J., Chaput, N., Puig, P. E., Novault, S., Escudier, B., Vivier, E., Lecesne, A., Robert, C., Blay, J. Y., Bernard, J., Caillat-Zucman, S., Freitas, A., Tursz, T., Wagner-Ballon, O., Capron, C., Vainchencker, W., Martin, F., Zitvogel, L. (2005) CD4+CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor-β-dependent manner. J. Exp. Med. 202, 1075-1085.
Chen, M. L., Pittet, M. J., Gorelik, L., Flavell, R. A., Weissleder, R., von Boehmer, H., Khazaie, K. (2005) Regulatory T cells suppress tumor-specific CD8 T cell cytotoxicity through TGF-β signals in vivo. Proc. Natl. Acad. Sci. USA 102, 419-424.
Peng, Y., Laouar, Y., Li, M. O., Green, E. A., Flavell, R. A. (2004) TGF-β regulates in vivo expansion of Foxp3-expressing CD4+CD25+ regulatory T cells responsible for protection against diabetes. Proc. Natl. Acad. Sci. USA 101, 4572-4577.
Graca, L., Le Moine, A., Cobbold, S. P., Waldmann, H. (2003) Dominant transplantation tolerance. Opinion. Curr. Opin. Immunol. 15, 499-506.
Akdis, M., Verhagen, J., Taylor, A., Karamloo, F., Karagiannidis, C., Crameri, R., Thunberg, S., Deniz, G., Valenta, R., Fiebig, H., Kegel, C., Disch, R., Schmidt-Weber, C. B., Blaser, K., Akdis, C. A. (2004) Immune responses in healthy and allergic individuals are characterized by a fine balance between allergen-specific T regulatory 1 and T helper 2 cells. J. Exp. Med. 199, 1567-1575.
Mills, K. H. (2004) Regulatory T cells: friend or foe in immunity to infection? Nat. Rev. Immunol. 4, 841-855.
Chehade, M., Mayer, L. (2005) Oral tolerance and its relation to food hypersensitivities. J. Allergy Clin. Immunol. 115, 3-12.
Akbari, O., Stock, P., DeKruyff, R. H., Umetsu, D. T. (2003) Role of regulatory T cells in allergy and asthma. Curr. Opin. Immunol. 15, 627-633.
Tsuji, N. M. (2006) Antigen-specific CD4(+) regulatory T cells in the intestine. Inflamm. Allergy Drug Targets. 5, 191-201.
Graca, L., Cobbold, S. P., Waldmann, H. (2002) Identification of regulatory T cells in tolerated allografts. J. Exp. Med. 195, 1641-1646.
Colovai, A. I., Mirza, M., Vlad, G., Wang, S., Ho, E., Cortesini, R., Suciu-Foca, N. (2003) Regulatory CD8+CD28- T cells in heart transplant recipients. Hum. Immunol. 64, 31-37.
Cortesini, R., Renna-Molajoni, E., Cinti, P., Pretagostini, R., Ho, E., Rossi, P., Suciu-Foca Cortesini, N. (2002) Tailoring of immunosuppression in renal and liver allograft recipients displaying donor specific T-suppressor cells. Hum. Immunol. 63, 1010-1018.
Liu, Z., Harris, P. E., Colovai, A. I., Reed, E. F., Maffei, A., Suciu-Foca, N. (1996) Indirect recognition of donor MHC Class II antigens in human transplantation. Clin. Immunol. Immunopathol. 78, 228-235.
Schaefer, C., Kim, G. G., Albers, A., Hoermann, K., Myers, E. N., Whiteside, T. L. (2005) Characteristics of CD4+CD25+ regulatory T cells in the peripheral circulation of patients with head and neck cancer. Br. J. Cancer 92, 913-920.
Ishibashi, Y., Tanaka, S., Tajima, K., Yoshida, T., Kuwano, H. (2006) Expression of Foxp3 in non-small cell lung cancer patients is significantly higher in tumor tissues than in normal tissues, especially in tumors smaller than 30 mm. Oncol. Rep. 15, 1315-1319.
Meloni, F., Morosini, M., Solari, N., Passadore, I., Nascimbene, C., Novo, M., Ferrari, M., Cosentino, M., Marino, F., Pozzi, E., Fietta, A. M. (2006) Foxp3 expressing CD4+ CD25+ and CD8+CD28- T regulatory cells in the peripheral blood of patients with lung cancer and pleural mesothelioma. Hum. Immunol. 67, 1-12.
Ormandy, L. A., Hillemann, T., Wedemeyer, H., Manns, M. P., Greten, T. F., Korangy, F. (2005) Increased populations of regulatory T cells in peripheral blood of patients with hepatocellular carcinoma. Cancer Res. 65, 2457-2464.
Kono, K., Kawaida, H., Takahashi, A., Sugai, H., Mimura, K., Miyagawa, N., Omata, H., Fujii, H. (2006) CD4(+)CD25high regulatory T cells increase with tumor stage in patients with gastric and esophageal cancers. Cancer Immunol. Immunother. 55, 1064-1071.
Kawaida, H., Kono, K., Takahashi, A., Sugai, H., Mimura, K., Miyagawa, N., Omata, H., Ooi, A., Fujii, H. (2005) Distribution of CD4+CD25high regulatory T-cells in tumor-draining lymph nodes in patients with gastric cancer. J. Surg. Res. 124, 151-157.
Okita, R., Saeki, T., Takashima, S., Yamaguchi, Y., Toge, T. (2005) CD4+CD25+ regulatory T cells in the peripheral blood of patients with breast cancer and non-small cell lung cancer. Oncol. Rep. 14, 1269-1273.
Leong, P. P., Mohammad, R., Ibrahim, N., Ithnin, H., Abdullah, M., Davis, W. C., Seow, H. F. (2006) Phenotyping of lymphocytes expressing regulatory and effector markers in infiltrating ductal carcinoma of the breast. Immunol. Lett. 102, 229-236.
Walsh, P. T., Benoit, B. M., Wysocka, M., Dalton, N. M., Turka, L. A., Rook, A. H. (2006) A role for regulatory T cells in cutaneous T-Cell lymphoma; induction of a CD4 + CD25 + Foxp3+ T-cell phenotype associated with HTLV-1 infection. J. Invest. Dermatol. 126, 690-692.
Voo, K. S., Peng, G., Guo, Z., Fu, T., Li, Y., Frappier, L., Wang, R. F. (2005) Functional characterization of EBV-encoded nuclear antigen 1-specific CD4+ helper and regulatory T cells elicited by in vitro peptide stimulation. Cancer Res. 65, 1577-1586.
Curiel, T. J., Coukos, G., Zou, L., Alvarez, X., Cheng, P., Mottram, P., Evdemon-Hogan, M., Conejo-Garcia, J. R., Zhang, L., Burow, M., Zhu, Y., Wei, S., Kryczek, I., Daniel, B., Gordon, A., Myers, L., Lackner, A., Disis, M. L., Knutson, K. L., Chen, L., Zou, W. (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat. Med. 10, 942-949.
Wang, T., Niu, G., Kortylewski, M., Burdelya, L., Shain, K., Zhang, S., Bhattacharya, R., Gabrilovich, D., Heller, R., Coppola, D., Dalton, W., Jove, R., Pardoll, D., Yu, H. (2004) Regulation of the innate and adaptive immune responses by Stat-3 signaling in tumor cells. Nat. Med. 10, 48-54.
Jarnicki, A. G., Lysaght, J., Todryk, S., Mills, K. H. (2006) Suppression of antitumor immunity by IL-10 and TGF-β-producing T cells infiltrating the growing tumor: influence of tumor environment on the induction of CD4+ and CD8+ regulatory T cells. J. Immunol. 177, 896-904.
Erdman, S. E., Sohn, J. J., Rao, V. P., Nambiar, P. R., Ge, Z., Fox, J. G., Schauer, D. B. (2005) CD4+CD25+ regulatory lymphocytes induce regression of intestinal tumors in ApcMin/+ mice. Cancer Res. 65, 3998-4004.
Erdman, S. E., Poutahidis, T., Tomczak, M., Rogers, A. B., Cormier, K., Plank, B., Horwitz, B. H., Fox, J. G. (2003) CD4+ CD25+ regulatory T lymphocytes inhibit microbially induced colon cancer in Rag2-deficient mice. Am. J. Pathol. 162, 691-702.
Tang, Q., Bluestone, J. A. (2006) Regulatory T-cell physiology and application to treat autoimmunity. Immunol. Rev. 212, 217-237.
Sugiyama, H., Gyulai, R., Toichi, E., Garaczi, E., Shimada, S., Stevens, S. R., McCormick, T. S., Cooper, K. D. (2005) Dysfunctional blood and target tissue CD4+CD25high regulatory T cells in psoriasis: mechanism underlying unrestrained pathogenic effector T cell proliferation. J. Immunol. 174, 164-173.
Cohen, J. L., Trenado, A., Vasey, D., Klatzmann, D., Salomon, B. L. (2002) CD4(+)CD25(+) immunoregulatory T Cells: new therapeutics for graft-versus-host disease. J. Exp. Med. 196, 401-406.
Marie, J. C., Letterio, J. J., Gavin, M., Rudensky, A. Y. (2005) TGF-β1 maintains suppressor function and Foxp3 expression in CD4+CD25+ regulatory T cells. J. Exp. Med. 201, 1061-1067.
Ermann, J., Hoffmann, P., Edinger, M., Dutt, S., Blankenberg, F. G., Higgins, J. P., Negrin, R. S., Fathman, C. G., Strober, S. (2005) Only the CD62L+ subpopulation of CD4+CD25+ regulatory T cells protects from lethal acute GVHD. Blood 105, 2220-2226.
Wysocki, C. A., Jiang, Q., Panoskaltsis-Mortari, A., Taylor, P. A., Mc-Kinnon, K. P., Su, L., Blazar, B. R., Serody, J. S. (2005) Critical role for CCR5 in the function of donor CD4+CD25+ regulatory T cells during acute graft-versus-host disease. Blood 106, 3300-3307.
Hackstein, H., Thomson, A. W. (2004) Dendritic cells: emerging pharmacological targets of immunosuppressive drugs. Nat. Rev. Immunol. 4, 24-34.
Rutella, S., Danese, S., Leone, G. (2006) Tolerogenic dendritic cells: cytokine modulation comes of age. Blood 108, 1435-1440.
Mahnke, K., Knop, J., Enk, A. H. (2003) Induction of tolerogenic DCs: 'you are what you eat'. Trends Immunol. 24, 646-651.
Harizi, H., Norbert, G. (2004) Inhibition of IL-6, TNF-α, and cyclooxygenase-2 protein expression by prostaglandin E2-induced IL-10 in bone marrow-derived dendritic cells. Cell. Immunol. 228, 99-109.
Adikari, S. B., Pettersson, A., Soderstrom, M., Huang, Y. M., Link, H. (2004) Interleukin-10-modulated immature dendritic cells control the proinflammatory environment in multiple sclerosis. Scand. J. Immunol. 59, 600-606.
Duan, R. S., Link, H., Xiao, B. G. (2005) Long-term effects of IFN-γ, IL-10, and TGF-β-modulated dendritic cells on immune response in Lewis rats. J. Clin. Immunol. 25, 50-56.
Wakkach, A., Fournier, N., Brun, V., Breittmayer, J. P., Cottrez, F., Groux, H. (2003) Characterization of dendritic cells that induce tolerance and T regulatory 1 cell differentiation in vivo. Immunity 18, 605-617.
Fujita, S., Seino, K., Sato, K., Sato, Y., Eizumi, K., Yamashita, N., Taniguchi, M., Sato, K. (2006) Regulatory dendritic cells act as regulators of acute lethal systemic inflammatory response. Blood 107, 3656-3664.
Gonzalez-Rey, E., Delgado, M. (2006) Therapeutic treatment of experimental colitis with regulatory dendritic cells generated with vasoactive intestinal peptide. Gastroenterology 131, 1799-1811.
Vosters, O., Neve, J., De Wit, D., Willems, F., Goldman, M., Verhasselt, V. (2003) Dendritic cells exposed to nacystelyn are refractory to maturation and promote the emergence of alloreactive regulatory t cells. Transplantation 75, 383-389.
Penna, G., Giarratana, N., Amuchastegui, S., Mariani, R., Daniel, K. C., Adorini, L. (2005) Manipulating dendritic cells to induce regulatory T cells. Microbes Infect. 7, 1033-1039.
Buckland, M., Jago, C., Fazekesova, H., George, A., Lechler, R., Lombardi, G. (2006) Aspirin modified dendritic cells are potent inducers of allo-specific regulatory T-cells. Int. Immunopharmacol. 6, 1895-1901.
Tan, P. H., Yates, J. B., Xue, S. A., Chan, C., Jordan, W. J., Harper, J. E., Watson, M. P., Dong, R., Ritter, M. A., Lechler, R. I., Lombardi, G., George, A. J. (2005) Creation of tolerogenic human dendritic cells via intracellular CTLA4: a novel strategy with potential in clinical immunosuppression. Blood 106, 2936-2943.
Tarbell, K. V., Petit, L., Zuo, X., Toy, P., Luo, X., Mqadmi, A., Yang, H., Suthanthiran, M., Mojsov, S., Steinman, R. M. (2007) Dendritic cell-expanded, islet-specific CD4+ CD25+ CD62L+ regulatory T cells restore normoglycemia in diabetic NOD mice. J. Exp. Med. 204, 191-201.
Den Boer, A. T., van Mierlo, G. J., Fransen, M. F., Melief, C. J., Offringa, R., Toes, R. E. (2005) CD4+ T cells are able to promote tumor growth through inhibition of tumor-specific CD8+ T-cell responses in tumor-bearing hosts. Cancer Res. 65, 6984-6989.
Van Mierlo, G. J., Boonman, Z. F., Dumortier, H. M., den Boer, A. T., Fransen, M. F., Nouta, J., van der Voort, E. I., Offringa, R., Toes, R. E., Melief, C. J. (2004) Activation of dendritic cells that cross-present tumor-derived antigen licenses CD8+ CTL to cause tumor eradication. J. Immunol. 173, 6753-6759.
Seya, T., Akazawa, T., Tsujita, T., Matsumoto, M. (2006) Role of Toll-like receptors in adjuvant-augmented immune therapies. Evid. Based Complement. Alternat. Med. 3, 31-38.
O'Neill, D., Bhardwaj, N. (2005) Exploiting dendritic cells for active immunotherapy of cancer and chronic infection. Methods Mol. Med. 109, 1-18.
Ribas, A. (2006) Update on immunotherapy for melanoma. J. Natl. Compr. Canc. Netw. 4, 687-694.
Nair, S., McLaughlin, C., Weizer, A., Su, Z., Boczkowski, D., Dannull, J., Vieweg, J., Gilboa, E. (2003) Injection of immature dendritic cells into adjuvant-treated skin obviates the need for ex vivo maturation. J. Immunol. 171, 6275-6282.
Kaufman, H. L., Disis, M. L. (2004) Immune system versus tumor: shifting the balance in favor of DCs and effective immunity. J. Clin. Invest. 113, 664-667.
Nair, S., Boczkowski, D., Fassnacht, M., Pisetsky, D., Gilboa, E. (2007) Vaccination against the forkhead family transcription factor Foxp3 enhances tumor immunity. Cancer Res. 67, 371-380.
