RELATIVE IMPORTANCE OF CD4(-CELL REPERTOIRES IN THE DEVELOPMENT OF ACUTE GRAFT-VERSUS-HOST DISEASE IN A MURINE MODEL OF BONE-MARROW TRANSPLANTATION() AND CD8(+) T)

T cell repertoire alterations occurring after allogeneic BMT and relat ed emergence of aGVHD has not been directly demonstrated, CD4, CD8 and V beta usage of T cells infiltrating spleen, lymph nodes and liver wa s 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 supera ntigens (SAgs) barriers according to experimental conditions, The earl y expansion in GVHD mice of CD4V beta 6(+) and of CD4V beta 3(+) T cel l subsets specific for Mtv-7 and Mtv-6 SAgs, respectively, is abolishe d in LS protected mice, By contrast, CD8(+) T cells infiltrate lymph n odes, the liver but not the spleen of LS as in GVHD mice, V beta subse t overexpression is frequent in all T cell phenotypes in GVHD but only among CD8(+) T cells in LS mice, Predominant V beta pattern subpopula tion is unique to each mouse, Overexpressed V beta subpopulation seque ncing clearly indicates that expansion results from a very limited num ber of clones, Association of a given V beta segment with different J beta for each mouse suggests that the response is directed towards man y different antigens, The data emphasize that Mtv-SAg and mHAgs CD4(+) T cells are of crucial importance during GVHD and that there is no re lationship between CD8(+) T cell repertoires and pathological status.