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

作者：Kawamura T^*; Kawachi Y; Kuwano Y; Sugahara S; Weerasinghe A; Kosaka T; Seki S; Abo T

来源：Scandinavian Journal of Immunology, 1999, 49(3): 258-268.

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 extrathymic origin), expanded in the liver and other organs, resulting in the induction of graft-versus-host disease (GVHD) with minor lymphocyte stimulating (M1s) disparity. When 6.5 Gy-irradiated BALB/c (H-2(d) M1s-1(b)2(a)) mice 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)) mice, 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 of V beta 3 and J beta 2.4. The majority of cells were confirmed to be of donor origin by the individual discrimination method, namely, they originated from isolated IL-2R beta(-)CD3(high) cells. Interestingly, these T cells lacked cytotoxicity against both a natural killer (NK)-sensitive target and thymocytes with M1s disparity and nondisparity. Another important finding was that activated granulocytes expanded at generalized sites in GVHD mice. The present results mise the possibility that M1s disparity is mainly recognized by TCRhigh cells with unique properties but that direct effector cells that induce GVHD might not De such T cells but rather accompanied granulocytes.

• 出版日期1999-3