[en] Interactions between B and CD4+ T cells are central to the pathogenesis of retrovirus-induced murine acquired immune deficiency virus (MAIDS). Prompted by previous work showing that treatment with cytotoxic T lymphocyte antigen 4 immunoglobulin (CTLA4Ig) partly inhibited the disease, we studied the course of infection in mice deficient for CD28-B7 interactions (mCTLA4-Hgamma1 transgenic mice). Despite a relative viral load identical to that of non-transgenic mice, the transgenic mice did not develop any of the major MAIDS symptoms (i.e. lymphoproliferation and immune anergy). The mCTLA4-Hgamma1 did not however, completely inhibit B-cell activation as indicated by a slight hypergammaglobulinaemia and microscopic blastic transformation. Absence of MAIDS in transgenic mice was associated with much lower levels of both interleukin-4 and interferon-gamma transcripts following viral infection. These results support the theory that the CD28/B7 costimulatory pathway is a critical determinant to MAIDS development.
Disciplines :
Immunology & infectious disease
Author, co-author :
de Leval, Laurence ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Debrus, S.
Lane, P.
Boniver, Jacques ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Moutschen, Michel ; Université de Liège - ULiège > Département des sciences cliniques > Immunopathologie - Transplantation
Language :
English
Title :
Mice Transgenic for a Soluble Form of Murine Cytotoxic T Lymphocyte Antigen 4 Are Refractory to Murine Acquired Immune Deficiency Sydrome Development
1. DUPLAN J.F., MONNOT P. & MISTRY P.B. (1970) [Leukemogenic activity of the mouse radioleukosis virus]. Bull Cancer 57, 23.
2. LEGRAND E., DACULSI R. & DUPLAN J.F. (1981) Characteristics of the cell populations involved in extra-thymic lymphosarcoma induced in C57BL/6 mice by RadLV-Rs. Leuk Res 5, 223.
3. CHATTOPADHYAY S.K., MORSE H.C., MAKINO M., RUSCETTI S.K. & HARTLEY J.W. (1989) Defective virus is associated with induction of murine retrovirus-induced immunodeficiency syndrome. Proc Natl Acad Sci USA 86, 3862.
4. AZIZ D.C., HANNA Z. & JOLICOEUR P. (1989) Severe immunodeficiency disease induced by a defective murine leukaemia virus. Nature 338, 505.
5. MOSIER D.E., YETTER R.A. & MORSE H.C. (1985) Retroviral induction of acute lymphoproliferative disease and profound immunosuppression in adult C57BL/6 mice. J Exp Med 161, 766.
6. HUANG M., SIMARD C., KAY D.G. & JOLICOEUR P. (1991) The majority of cells infected with the defective murine AIDS virus belong to the B-cell lineage. J Virol 65, 6562.
7. YETTER R.A., BULLER R.M., LEE J.S. et al. (1988) CD4+ T cells are required for development of a murine retrovirus-induced immunodeficiency syndrome (MAIDS). J Exp Med 168, 623.
8. GIESE N.A., GIESE T. & MORSE H.C. (1994) Murine AIDS is an antigen-driven disease: requirements for major histocompatibility complex class II expression and CD4+ T cells. J Virol 68, 5819.
9. MAKINO M., YOSHIMATSU K., AZUMA M. et al. (1995) Rapid development of murine AIDS is dependent of signals provided by CD54 and CD11a. J Immunol 155, 974.
10. GREEN K.A., CRASSI K.M., LAMAN J.D. et al. (1996) Antibody to the ligand for CD40 (gp39) inhibits murine AIDS-associated splenomegaly, hypergammaglobulinemia, and immunodeficiency in disease-susceptible C57BL/6 mice. J Virol 70, 2569.
11. GREEN K.A., NOELLE R.J. & GREEN W.R. (1998) Evidence for a continued requirement for CD40/CD40 ligand (CD154) interactions in the progression of LP-BM5 retrovirus-induced murine AIDS. Virology 241, 260.
12. BOUSSIOTIS V.A., FREEMAN G.J., GRIBBEN J.G. & NADLER L.M. (1996) The role of B7/B7: CD28/CLTA-4 pathways in the prevention of anergy, induction of productive immunity and down-regulation of the immune response. Immunol Rev 153, 5.
13. JUNE C.H., BLUESTONE J.A., NADLER L.M. & THOMPSON C.B. (1994) The B7 and CD28 receptor families. Immunol Today 15, 321.
14. DE LEVAL L., COLOMBI S., DEBRUS S. et al. (1998) CD28 B7 costimulatory blockade by CTLA4Ig delays the development of retrovirus-induced murine AIDS. J Virol 72, 5285.
15. LINSLEY P.S., WALLACE P.M., JOHNSON J. et al. (1992) Immunosuppression in vivo by a soluble form of the CTLA-4 T cell activation molecule. Science 257, 792.
16. LANE P., BURDET C., HUBELE S. et al. (1994) B cell function in mice transgenic for mCTLA4-H gamma 1: lack of germinal centers correlated with poor affinity maturation and class switching despite normal priming of CD4+ T cells. J Exp Med 179, 819.
17. HUANG M., SIMARD C. & JOLICOEUR P. (1989) Immunodeficiency and clonal growth of target cells induced by helper-free defective retrovirus. Science 246, 1614.
19. SUZUKI K. & FUJIWARA M. (1995) [Exocrinopathy resembling Sjogren's syndrome induced by a murine retrovirus]. Nippon Rinsho 53, 2461.
20. SVETIC A., FINKELMAN F.D., JIAN Y.C. et al. (1991) Cytokine gene expression after in vivo primary immunization with goat antibody to mouse IgD antibody. J Immunol 147, 2391.
21. SASSEN A., VANDER P.F., JANOWSKI M. & MAISIN J.R. (1974) Immunoglobulin analysis of C57BL mice infected with a radiation-induced leukemia virus. J Natl Cancer Inst 52, 539.
22. PATTENGALE P.K., TAYLOR C.R., TWOMEY P. et al. (1982) Immunopathology of B-cell lymphomas induced in C57BL/6 mice by dualtropic murine leukemia virus (MuLV). Am J Pathol 107, 362.
23. HOLMES K.L., MORSE H.C., MAKINO M., HARDY R.R. & HAYAKAWA K. (1990) A unique subset of normal murine CD4+ T cells lacking Thy-1 is expanded in a murine retrovirus-induced immunodeficiency syndrome, MAIDS. Eur J Immunol 20, 2783.
24. MOUTSCHEN M.P., COLOMBI S., DEPREZ M. et al. (1994) Population dynamics of CD4+ T cells lacking Thy-1 in murine retrovirus-induced immunodeficiency syndrome (MAIDS). Scand J Immunol 39, 216.
25. HUANG M., SIMARD C. & JOLICOEUR P. (1992) Susceptibility of inbred strains of mice to murine AIDS (MAIDS) correlates with target cell expansion and high expression of defective MAIDS virus. J Virol 66, 2398.
26. LIU Y.J., ZHANG J., LANE P.J., CHAN E.Y. & MACLENNAN I.C. (1991) Sites of specific B cell activation in primary and secondary responses to T cell-dependent and T cell-independent antigens [published erratum appears in Eur J Immunol 1992 February; 22 (2): 615]. Eur J Immunol 21, 2951.
27. ZHENG B., HAN S. & KELSOE G. (1996) T helper cells in murine germinal centers are antigen-specific emigrants that downregulate Thy-1. J Exp Med 184, 1083.
28. YU P., MORAWETZ R.A., CHATTOPADHYAY S., MAKINO M., KISHIMOTO T. & KIKUTANI H. (1999) CD40-deficient mice infected with the defective murine leukemia virus LP-BM5def do not develop murine AIDS but produce IgE and IgG1 in vivo. Eur J Immunol 29, 615.
29. CARDELL S., MERKENSCHLAGER M., BODMER H. et al. (1994) The immune system of mice lacking conventional MHC class II molecules. Adv Immunol 55, 423.
30. KAWABE T., NAKA T., YOSHIDA K. et al. (1994) The immune responses in CD40-deficient mice: impaired immunoglobulin class switching and germinal center formation. Immunity 1, 167.
31. AL HARTHI L., ROEBUCK K.A. & LANDAY A. (1998) Induction of HIV-1 replication by type 1-like cytokines, interleukin (IL) -12 and IL-15: effect on viral transcriptional activation, cellular proliferation, and endogenous cytokine production. J Clin Immunol 18, 124.
32. ZIMMERMANN C., SEILER P., LANE P. & ZINKERNAGEL R.M. (1997) Antiviral immune responses in CTLA4 transgenic mice. J Virol 71, 1802.
33. WU Y., ZHOU Q., ZHENG P. & LIU Y. (1998) CD28-independent induction of T helper cells and immunoglobulin class switches requires costimulation by the heat-stable antigen. J Exp Med 187, 1151.
34. KHOURY S.J., AKALIN E., CHANDRAKER A. et al. (1995) CD28-B7 costimulatory blockade by CTLA4Ig prevents actively induced experimental autoimmune encephalomyelitis and inhibits Th1 but spares Th2 cytokines in the central nervous system. J Immunol 155, 4521.
35. KANAGAWA O., VAUPEL B.A., GAYAMA S., KOEHLER G. & KOPF M. (1993) Resistance of mice deficient in IL-4 to retrovirus-induced immunodeficiency syndrome (MAIDS) [see comments]. Science 262, 240.
37. MORSE H.C., GIESE N., MORAWETZ R. et al. (1995) Cells and cytokines in the pathogenesis of MAIDS, a retrovirus-induced immunodeficiency syndrome of mice. Springer Semin Immunopathol 17, 231.
38. GAZZINELLI R.T., GIESE N.A. & MORSE H.C. (1994) In vivo treatment with interleukin 12 protects mice from immune abnormalities observed during murine acquired immunodeficiency syndrome (MAIDS). J Exp Med 180, 2199.
39. PADRID P.A., MATHUR M., LI X. et al. (1998) CTLA4Ig inhibits airway eosinophilia and hyperresponsiveness by regulating the development of Th1/Th2 subsets in a murine model of asthma. Am J Respir Cell Mol Biol 18, 453.
40. SHANAFELT M.C., KANG I., BARTHOLD S.W. & BOCKENSTEDT L.K. (1998) Modulation of murine Lyme borreliosis by interruption of the B7/CD28 T-cell costimulatory pathway. Infect Immun 66, 266.
41. ANDREWS C., SWAIN S.L. & MURALIDHAR G. (1997) CD4 T cell anergy in murine AIDS: costimulation via CD28 and the addition of IL-12 are not sufficient to rescue anergic CD4 T cells. J Immunol 159, 2132.
