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

Abstract

T cell repertoire alterations occurring after allogeneic BMT and related emergence of aGVHD has not been directly demonstrated. CD4, CD8 and Vβ usage of T cells infiltrating spleen, lymph nodes and liver was compared in lethally irradiated F1(DBA/2 × 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 superantigens (SAgs) barriers according to experimental conditions. The early expansion in GVHD mice of CD4Vβ6⁺ and of CD4Vβ3⁺ 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. Vβ subset overexpression is frequent in all T cell phenotypes in GVHD but only among CD8⁺ T cells in LS mice. Predominant Vβ pattern subpopulation is unique to each mouse. Overexpressed Vβ subpopulation sequencing clearly indicates that expansion results from a very limited number of clones. Association of a given Vβ segment with different Jβ 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.