Tomiyama K, Watanabe H, Seki S, Ito M, Abo T
Department of Immunology, Niigata University School of Medicine, Japan.
Clin Exp Immunol. 1998 May;112(2):196-204. doi: 10.1046/j.1365-2249.1998.00591.x.
TCRhigh cells are generated by the mainstream of T cell differentiation in the thymus, whereas TCRint cells (or NK1.1+ T cells) are generated extrathymically in the liver and by an alternative intrathymic pathway. It is still unknown how these T cell populations interact in vivo with each other. To investigate the interaction of TCRint cells with TCRhigh cells, we used congenitally athymic nude (B6-nu/nu) mice which carry only TCRint cells in all immune organs. When TCRhigh cells from B6-C-H-2bm12 (bm12) mice (i.e. I-Abm12) were injected into B6-nu/nu mice (i.e. 1-Ab), the expanding T cell population was a mixture of TCRhigh cells of donor origin and TCRint cells of recipient origin. However, 9 Gy-irradiated nude mice permitted a full expansion of TCRhigh cells which expressed the IL-2Ralpha+beta+ phenotype, namely, they were at the most activated state. These mice died of acute graft-versus-host disease (GVHD) within 5 days. On the other hand, non-irradiated nude mice suppressed the expansion of TCRhigh cells of donor origin and such TCRhigh cells continued to have the IL-2Ralpha(+/-)beta+ phenotype. These mice could survive but showed signs of chronic GVHD thereafter. In both situations, CD4+alphabeta T cells expanded irrespective of donor or recipient origin. These results suggest that TCRint cells in the recipient mice possess a regulatory function in relation to donor TCRhigh cells; as a result, fully activated TCRhigh cells acquired the IL-2Ralpha+beta+ phenotype and injured the host, but TCRhigh cells suppressed in vivo remained as the IL-2Ralpha(+/-)beta+ phenotype and only partially injured the host.
TCR高表达细胞由胸腺中T细胞分化的主流途径产生，而TCR中等表达细胞（或NK1.1+ T细胞）在肝脏中通过胸腺外途径以及胸腺内的另一条途径产生。目前仍不清楚这些T细胞群体在体内如何相互作用。为了研究TCR中等表达细胞与TCR高表达细胞的相互作用，我们使用了先天性无胸腺的裸鼠（B6-nu/nu），其所有免疫器官中仅携带TCR中等表达细胞。当将来自B6-C-H-2bm12（bm12）小鼠（即I-Abm12）的TCR高表达细胞注射到B6-nu/nu小鼠（即1-Ab）中时，扩增的T细胞群体是供体来源的TCR高表达细胞和受体来源的TCR中等表达细胞的混合物。然而，接受9 Gy照射的裸鼠允许TCR高表达细胞充分扩增，这些细胞表达IL-2Rα+β+表型，即它们处于最活化状态。这些小鼠在5天内死于急性移植物抗宿主病（GVHD）。另一方面，未照射的裸鼠抑制了供体来源的TCR高表达细胞的扩增，并且这种TCR高表达细胞继续具有IL-2Rα(+/-)β+表型。这些小鼠可以存活，但此后表现出慢性GVHD的迹象。在这两种情况下，CD4+αβ T细胞无论供体或受体来源均会扩增。这些结果表明，受体小鼠中的TCR中等表达细胞对供体TCR高表达细胞具有调节功能；因此，完全活化的TCR高表达细胞获得IL-2Rα+β+表型并损伤宿主，但在体内受到抑制的TCR高表达细胞保持IL-2Rα(+/-)β+表型，仅对宿主造成部分损伤。
