Kawamura T, Kawachi Y, Kuwano Y, Sugahara S, Weerasinghe A, Kosaka T, Seki S, Abo T
Department of Immunology, Niigata University School of Medicine, Japan.
Scand J Immunol. 1999 Mar;49(3):258-68. doi: 10.1046/j.1365-3083.1999.00497.x.
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-2d M1s-1b2a) mice were injected with interleukin-2 receptor beta-chain(-) (IL-2Rbeta(-)) CD3high cells purified from the spleen of B10.D2 (H-2d M1s-1b2b) mice, IL-2Rbeta(+)CD3high cells expanded in the liver and other organs of recipient mice. The majority of these cells were found to be IL-2Ralpha(-)Mel-14(-)CD4(+)Vbeta3(+) in GVHD mice. The CDR3 region in their TCR-alphabeta (i.e. N-Dbeta-N) was polyclonal, although there were skewed usages of Vbeta3 and Jbeta2.4. The majority of cells were confirmed to be of donor origin by the individual discrimination method, namely, they originated from isolated IL-2Rbeta(-)CD3high 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 TCRhigh cells with unique properties but that direct effector cells that induce GVHD might not be such T cells but rather accompanied granulocytes.
在本研究中，我们调查了哪种类型的T细胞：高T细胞受体（TCRhigh，胸腺来源的细胞）或中等TCR（TCRint，胸腺外来源的细胞），在肝脏和其他器官中扩增，从而在微小淋巴细胞刺激（Mls）不相容的情况下导致移植物抗宿主病（GVHD）。当给经6.5 Gy照射的BALB/c（H-2d Mls-1b2a）小鼠注射从B10.D2（H-2d Mls-1b2b）小鼠脾脏中纯化的白细胞介素-2受体β链（-）（IL-2Rβ（-））CD3high细胞时，IL-2Rβ（+）CD3high细胞在受体小鼠的肝脏和其他器官中扩增。在GVHD小鼠中发现这些细胞的大多数是IL-2Rα（-）Mel-14（-）CD4（+）Vβ3（+）。它们的TCR-αβ中的CDR3区域（即N-Dβ-N）是多克隆的，尽管Vβ3和Jβ2.4的使用存在偏差。通过个体鉴别方法证实这些细胞的大多数是供体来源的，也就是说，它们起源于分离的IL-2Rβ（-）CD3high细胞。有趣的是，这些T细胞对自然杀伤（NK）敏感靶细胞和具有Mls不相容和相容的胸腺细胞均缺乏细胞毒性。另一个重要发现是活化的粒细胞在GVHD小鼠的全身部位扩增。目前的结果提出了一种可能性，即Mls不相容主要由具有独特特性的TCRhigh细胞识别，但诱导GVHD的直接效应细胞可能不是此类T细胞，而是伴随的粒细胞。
