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Mechanisms Involved in Graft‐Versus‐Host Disease Induced by the Disparity of Minor Histocompatibility M1s Antigens
Author(s) -
Toshihiko Kawamura,
Yasuyuki Kawachi,
Yuh Kuwano,
Satoshi Sugahara,
Anura Weerasinghe,
Takayuki Kosaka,
Shu Seki,
Toru Abo
Publication year - 1999
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.1999.00497.x
Subject(s) - cd3 , biology , t cell receptor , immunology , antigen , natural killer t cell , interleukin 21 , t cell , graft versus host disease , microbiology and biotechnology , immune system , cd8 , stem cell
In this study we investigated which type of T cells: high T‐cell receptor (TCR high , cells of thymic origin) or intermediate TCR (TCR int , 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 β‐chain − (IL‐2Rβ − ) CD3 high cells purified from the spleen of B10.D2 (H‐2 d M1s‐1 b 2 b ) mice, IL‐2Rβ + CD3 high cells expanded in the liver and other organs of recipient mice. The majority of these cells were found to be IL‐2Rα − Mel‐14 − CD4 + Vβ3 + in GVHD mice. The CDR3 region in their TCR‐αβ (i.e. N–Dβ–N) was polyclonal, although there were skewed usages of Vβ3 and Jβ2.4. The majority of cells were confirmed to be of donor origin by the individual discrimination method, namely, they originated from isolated IL‐2Rβ − 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 raise the possibility that M1s disparity is mainly recognized by TCR high cells with unique properties but that direct effector cells that induce GVHD might not be such T cells but rather accompanied granulocytes.