[en] Immunity to Nippostrongylus brasiliensis reinfection requires pulmonary CD4+ T-cell responses. We examined whether secondary lymphoid recruited or pre-existing lung CD4+ T-cell populations coordinated this immunity. To do this, we blocked T-cell egress from lymph nodes using Fingolimod (FTY720). This impaired host ability to resolve a primary infection but did not change effectiveness of recall immunity. Associated with this effective recall immunity was the expansion and T helper type 2 polarization of a pre-existing pulmonary CD4+ T-cell population. LTbetaR-Ig (lymphotoxin beta-receptor fusion protein)-mediated disruption of stromal cell organization of immune cells did not disrupt this recall immunity, suggesting that protection was mediated by a pulmonary interstitial residing CD4+ T-cell population. Adoptive transfer of N. brasiliensis-experienced pulmonary CD4+ T cells from FTY720-treated wild-type or T-cell interleukin (IL)-4Ralpha-deficient mice demonstrated protection to be IL-4Ralpha dependent. These results show that pre-existing CD4+ T cells can drive effective recall immunity to N. brasiliensis infection independently of T-cell recruitment from secondary lymphoid organs.Mucosal Immunology advance online publication 19 June 2013; doi:10.1038/mi.2013.40.
Disciplines :
Immunology & infectious disease
Author, co-author :
Thawer, S. G.
Horsnell, W. Gc
Darby, M.
Hoving, J. C.
Dewals, Benjamin G ; Université de Liège - ULiège > Immunologie et vaccinologie
Cutler, A. J.
Lang, D.
Brombacher, F.
Language :
English
Title :
Lung-resident CD4 T cells are sufficient for IL-4Ralpha-dependent recall immunity to Nippostrongylus brasiliensis infection.
Publication date :
March 2014
Journal title :
Mucosal Immunology
ISSN :
1933-0219
eISSN :
1935-3456
Publisher :
Nature Publishing Group, New York, United States - New York
Hotez, P.J., Brindley, P.J., Bethony, J.M., King, C.H., Pearce, E.J. & Jacobson, J. Helminth infections: The great neglected tropical diseases. J. Clin. Invest. 118, 1311-1321 (2008).
Horsnell, W.G.C. et al. Delayed goblet cell hyperplasia, acetylcholine receptor expression, and worm expulsion in SMC-specific IL-4Ralphadeficient mice. PLoS pathog. 3, e1 (2007).
Kopf, M., Le Gros, G., Bachmann, M., Lamers, M.C., Bluethmann, H. & Kohler, G. Disruption of the murine IL-4 gene blocks Th2 cytokine responses. Nature 362, 245-248 (1993).
Brombacher, F. The role of interleukin-13 in infectious diseases and allergy. BioEssays. 22, 646-656 (2000).
Urban, J.F. Jr., Noben-Trauth,N., Schopf, L.,Madden, K.B. & Finkelman, F.D. Cutting edge: IL-4 receptor expression by non-bone marrow-derived cells is required to expel gastrointestinal nematode parasites. J. Immunol. 167, 6078-6081 (2001).
Horsnell, W.G.C. et al. IL-4Ra-responsive smooth muscle cells contribute to initiation of TH2 immunity and pulmonary pathology in Nippostrongylus brasiliensis infections. Mucosal. Immunol. 4, 83-92 (2011).
Harvie, M., Camberis, M., Tang, S.-C., Delahunt, B., Paul,W. & LeGros, G. The lung is an important site for priming CD4 T-cell-mediated protective immunity against gastrointestinal helminth parasites. Infect. Immun. 78, 3753-3762 (2010).
Anthony, R.M. et al. Memory TH2 cells induce alternatively activated macrophages to mediate protection against nematode parasites. Nat. Med. 12, 955-960 (2007).
Sallusto, F., Geginat, J. & Lanzavecchia, A. Central memory and effector memory Tcell subsets: Function, generation, and maintenance. Annu. Rev. Immunol. 22, 745-763 (2004).
Katona, I.M., Urban, J.F. Jr.& Finkelman, F. The role of L3T4+ and LYT-2+ T cells in the IgE response and immunity to Nippostrongylus brasiliensis. J. Immunol. 140, 3206-3211 (1988).
Connor, L.M. et al. A key role for lung-resident memory lymphocytes in protective immune responses after BCG vaccination. Eur. J. Immunol. 40, 2482-2492 (2010).
Harris, N.L.,Watt, V., Ronchese, F. & Le Gros, G. Differential Tcell function and fate in lymph node and nonlymphoid tissues. J. Exp. Med. 195, 317-326 (2002).
Hogan, B.R.J., Zhong,W., Usherwood, E.J., Cookenham, T., Roberts, A.D. & Woodland, D.L. Protection from respiratory virus infections can be mediated by antigen-specific CD4 T Cells that persist in the lungs. J. Exp. Med. 193, 0-5 (2001).
Teijaro, J.R., Turner, D., Pham, Q., Wherry, E.J., Lefranc'ois, L. & Farber, D.L. Cutting edge: Tissue-retentive lung memory CD4 T cells mediate optimal protection to respiratory virus infection. J. Immunol. 187, 5510-5514 (2011).
Zaph, C., Rook, K.A., Goldschmidt, M., Mohrs, M., Scott, P. & Artis, D. Persistence and function of central and effector memory CD4+ T cells following infection with a gastrointestinal helminth. J. Immunol. 177, 511-518 (2006).
Van Panhuys, N., Perret, R., Prout, M., Ronchese, F. & Le Gros, G. Effector lymphoid tissue and its crucial role in protective immunity. Trends Immunol. 26, 242-247 (2005).
Chiba, K., Matsuyuki, H., Maeda, Y. & Sugahara, K. Role of sphingosine 1-phosphate receptor type 1 in lymphocyte egress from secondary lymphoid tissues and thymus. Cell. Mol. Immunol. 3, 11-19 (2006).
Hofmann, M., Brinkmann, V. & Zerwes, H.-G. FTY720 preferentially depletes naive T cells from peripheral and lymphoid organs. Int. Immunopharmacol. 6, 1902-1910 (2006).
Mearns, H. et al. Interleukin-4-promoted T helper 2 responses enhance Nippostrongylus brasiliensis-induced pulmonary pathology. Infect. Immun. 76, 5535-5542 (2008).
Lohning, M. et al. T1/ST2 is preferentially expressed on murine Th2 cells, independent of interleukin 4, interleukin 5, and interleukin 10, and important for Th2 effector function. Proc. Natl. Acad. Sci. USA 95, 6930-6935 (1998).
Sullivan, B.M. et al. Genetic analysis of basophil function in vivo. Nat. Immunol. 12, 527-535 (2011).
Browning, J.L. Inhibition of the lymphotoxin pathway as a therapy for autoimmune disease. Immunol. Rev. 223, 202-220 (2008).
Fava, R.A. et al. A role for the lymphotoxin/LIGHT axis in the pathogenesis of murine collagen-induced arthritis. J Immunol. 171, 115-126 (2003).
Van de Pavert, S.A. & Mebius, R.E. New insights into the development of lymphoid tissues. Nat. Rev. Immunol. 10, 664-674 (2010).
Fava, R. et al. Lymphotoxin-beta receptor blockade reduces CXCL13 in lacrimal glands and improves corneal integrity in the NOD model of sjogren's syndrome. Arthritis Res. & Ther. 13, R182 (2011).
Hasnain, S.Z. et al. Muc5ac: A critical componentmediating the rejection of enteric nematodes. J. Exp. Med. 208, 893-900 (2011).
Barner, M., Mohrs, M., Brombacher, F. & Kopf, M. Differences between IL-4R alpha-deficient and IL-4-deficient mice reveal a role for IL-13 in the regulation of Th2 responses. Curr. Biol. 8, 669-672 (1998).
Herbert, D.R. et al. Alternative macrophage activation is essential for survival during schistosomiasis and downmodulates T helper 1 responses and immunopathology. Immunity 20, 623-635 (2004).
Chapman, T.J., Lambert, K. & Topham, D.J. Rapid reactivation of extralymphoid CD4 T cells during secondary infection. PloS One 6, e20493 (2011).
Masopust, D., Vezys, V., Marzo, A.L. & Lefranc'ois, L. Preferential localization of effector memory cells in nonlymphoid tissue. Science 291, 2413-2417 (2001).
Moyron-Quiroz, J.E. et al. Persistence and responsiveness of immunologic memory in the absence of secondary lymphoid organs. Immunity 25, 643-654 (2006).
Hogan, R.J. et al. Activated antigen-specific CD8+ T cells persist in the lungs following recovery from respiratory virus infections. J. Immunol. 166, 1813-1822 (2001).
Hogan, R.J. et al. Long-term maintenance of virus-specific effector memory CD8+ T cells in the lung airways depends on proliferation. J. Immunol. 169, 4976-4981 (2002).
Moyron-Quiroz, J.E. et al. Role of inducible bronchus associated lymphoid tissue (iBALT) in respiratory immunity. Nat. Med. 10, 927-934 (2004).
Randall, T.D. Bronchus-associated lymphoid tissue (BALT) structure and function. Adv. Immunol. 107, 187-241 (2010).
Hofmann, J., Greter,M., Du Pasquier, L. & Becher, B. B-cells need a proper house, whereas T-cells are happy in a cave; the dependence of lymphocytes on secondary lymphoid tissues during evolution. Trends Immunol. 31, 144-153 (2010).
Wakim, L.M., Waithman, J., Van Rooijen, N., Heath, W.R. & Carbone, F.R. Dendritic cell-induced memory T cell activation in nonlymphoid tissues. Science 319, 198-202 (2008).
Constant, S.L. et al. Resident lung antigen-presenting cells have the capacity to promote Th2 T cell differentiation in situ. J. Clin. Invest. 110, 1441-1448 (2002).
Dewals, B. et al. IL-4Ralpha responsiveness of non-CD4 T cells contributes to resistance in Schistosoma mansoni infection in pan-T cell-specific IL-4Ralpha-deficient mice. Am. J. Pathol. 175, 706-716 (2009).