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.