Hakim F T, Payne S, Shearer G M
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
J Immunol. 1994 Jan 1;152(1):58-64.
We previously have observed that T dependent immune functions were deficient for several months after induction of acute suppressive graft-vs-host-reaction (GVHR) by injection of parental C57BL/10 donor spleen cells into unirradiated (B10 x B10.BR) F, hosts. We therefore investigated whether new T cells matured after acute GVHR, and whether these were tolerant of host Ag. By 8 to 17 mo after GVHR, the frequencies of splenic CD4 and CD8 T cells were found to be comparable to age-matched untreated hosts, although the lymphoid organ size and hence the total number of T cells was significantly reduced. When GVHR was induced with a combination of C57BL/6 (Thy-1.2) mature lymphocytes and B6.PL (Thy-1.1) bone marrow stem cells, the mature donor Thy-1.2 T cells initially predominated during the acute GVHR. After several months, however, 75% of the CD4 and 50% of the CD8 T cell population was derived from donor Thy-1.1% pre-T cells that had matured in the host. Long term GVHR spleen cells were unresponsive to host Ag in CTL assays, but did not suppress anti-host CTL responses. Finally, host-reactive V beta 11 TCR expressing cells were found to be clonally deleted from splenic CD4 and CD8 populations, consistent with intrathymic negative selection. This evidence suggests that the post-GVHR thymus has the capacity to produce and negatively select phenotypically mature CD4 and CD8 T cells and that a failure to clonally delete self-reactive populations is not a contributing factor to the development of chronic GVHR in this system.
我们之前观察到，通过向未受照射的（B10×B10.BR）F1宿主注射亲代C57BL/10供体脾细胞诱导急性抑制性移植物抗宿主反应（GVHR）后，T细胞依赖性免疫功能在数月内存在缺陷。因此，我们研究了急性GVHR后是否有新的T细胞成熟，以及这些细胞是否对宿主抗原具有耐受性。在GVHR后8至17个月，发现脾脏CD4和CD8 T细胞的频率与年龄匹配的未处理宿主相当，尽管淋巴器官大小以及因此T细胞总数显著减少。当用C57BL/6（Thy-1.2）成熟淋巴细胞和B6.PL（Thy-1.1）骨髓干细胞联合诱导GVHR时，成熟的供体Thy-1.2 T细胞在急性GVHR期间最初占主导地位。然而，几个月后，75%的CD4和50%的CD8 T细胞群体来自于在宿主体内成熟的供体Thy-1.1%前T细胞。长期GVHR脾细胞在CTL试验中对宿主抗原无反应，但不抑制抗宿主CTL反应。最后，发现表达宿主反应性Vβ11 TCR的细胞从脾脏CD4和CD8群体中克隆性缺失，这与胸腺内阴性选择一致。这一证据表明，GVHR后的胸腺有能力产生并对表型成熟的CD4和CD8 T细胞进行阴性选择，并且未能克隆性删除自身反应性群体不是该系统中慢性GVHR发展的促成因素。
