Mechanisms involved in graft-versus-host disease induced by the disparity of minor histocompatibility Mls antigens

In this study we investigated which type of T cells: high T-cell receptor ( TCRhigh, cells of thymic origin) or intermediate TCR (TCRint, cells of extr athymic origin), expanded in the liver and other organs, resulting in the i nduction of graft-versus-host disease (GVHD) with minor lymphocyte stimulat ing (M1s) disparity. When 6.5 Gy-irradiated BALB/c (H-2(d) M1s-1(b)2(a)) mi ce were injected with interleukin-2 receptor beta-chain(-) (IL-2R beta(-)) CD3(high) cells purified from the spleen of B10.D2 (H-2(d) M1s-1(b)2(b)) mi ce, IL-2R beta(+)CD3(high) cells expanded in the liver and other organs of recipient mice, The majority of these cells were found to be IL-2R alpha(-) Mel-14(-)CD4(+)V beta 3(+) in GVHD mice. The CDR3 region in their TCR-alpha beta (i.e. N-D beta-N) was polyclonal, although there were skewed usages o f V beta 3 and J beta 2.4. The majority of cells were confirmed to be of do nor origin by the individual discrimination method, namely, they originated from isolated IL-2R beta(-)CD3(high) cells. Interestingly, these T cells l acked cytotoxicity against both a natural killer (NK)-sensitive target and thymocytes with M1s disparity and nondisparity. Another important finding w as that activated granulocytes expanded at generalized sites in GVHD mice. The present results mise the possibility that M1s disparity is mainly recog nized by TCRhigh cells with unique properties but that direct effector cell s that induce GVHD might not De such T cells but rather accompanied granulo cytes.