Relative importance of CD4+ and CD8+ T cell repertoires in the development of acute graft-versus-host disease in a murine model of bone marrow transplantation.
T cell repertoire alterations occurring after allogeneic BMT and related emergence of aGVHD has not been directly demonstrated. CD4, CD8 and Vbeta usage of T cells infiltrating spleen, lymph nodes and liver was compared in lethally irradiated F1(DBA/2 x B10.D2) recipients which develop (GVHD mice) or not (long survivor:LS mice) aGVHD across minor histocompatibility antigens (mHAgs) and Mtv-6 and Mtv-7 encoded super-antigens (SAgs) barriers according to experimental conditions. The early expansion in GVHD mice of CD4Vbeta6+ and of CD4Vbeta3+ T cell subsets specific for Mtv-7 and Mtv-6 SAgs, respectively, is abolished in LS protected mice. By contrast, CD8+ T cells infiltrate lymph nodes, the liver but not the spleen of LS as in GVHD mice. Vbeta subset overexpression is frequent in all T cell phenotypes in GVHD but only among CD8+ T cells in LS mice. Predominant Vbeta pattern subpopulation is unique to each mouse. Overexpressed Vbeta subpopulation sequencing clearly indicates that expansion results from a very limited number of clones. Association of a given Vbeta segment with different Jbeta for each mouse suggests that the response is directed towards many different antigens. The data emphasize that Mtv-SAg and mHAgs CD4+ T cells are of crucial importance during GVHD and that there is no relationship between CD8+ T cell repertoires and pathological status.
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INSERM U.267, Villejuif, France.
de La Selle
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Bruley-Rosset
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D000818:Animals; D000954:Antigens, Surface / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D016026:Bone Marrow Transplantation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology; D008099:Liver / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008324:Mammary Tumor Virus, Mouse / Q000276:immunology; D051379:Mice; D008811:Mice, Inbred DBA; D015778:Minor Histocompatibility Antigens / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology
D000954:Antigens, Surface; D000956:Antigens, Viral; D015778:Minor Histocompatibility Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta