Lake J P, Kapp J A, Pierce C W
Department of Pathology and Laboratory Medicine, Jewish Hospital of St. Louis, MO.
J Immunol. 1988 May 15;140(10):3296-302.
A Ts cell subset has been identified in the spleens of responder mice 3 to 6 wk after immunization with an optimally immunogenic dose of L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT). These Ts were positively selected by panning procedures by using a mAb (1248 A4.10) produced by immunization of rats with semipurified mouse GAT-specific, single polypeptide chain suppressor factor. These Ts cells inhibited the activity of virgin Th cells but not memory Th cells and this activity was genetically restricted by genes which are linked to the Ig H chain (Igh) locus on chromosome 12. Use of the Igh recombination strain, BAB.14, which has a crossover near the VHCH region junction, demonstrated that the genes regulating the Igh restriction map telomeric to the VH genes. The Igh-linked restriction regulated the interaction of A4.10+ Ts cells with virgin T cells and not B cells. However, A4.10+ Ts did not act directly on Lyt-2-Th cells, but required the presence of Lyt-2+ cells for suppression. Suppression by GAT-primed A4.10+-Ts cells also required syngenicity at Igh-linked genes by both Lyt-2- and Lyt-2+ T cells. These results indicated that A4.10+-Ts cells were inducer Ts cells which activated Lyt-2+ effector Ts cells which prevented primary GAT specific Th cell activity. The interaction between A4.10+-Ts inducer and effector Ts cells and/or the interaction of the effector Ts and its target cell were restricted by genes linked to the Igh constant region.
在用最佳免疫原剂量的L-谷氨酸60-L-丙氨酸30-L-酪氨酸10（GAT）免疫后3至6周，在反应小鼠的脾脏中鉴定出一个调节性T细胞亚群。通过使用由用半纯化的小鼠GAT特异性单多肽链抑制因子免疫大鼠产生的单克隆抗体（1248 A4.10）进行淘选程序，对这些调节性T细胞进行阳性选择。这些调节性T细胞抑制处女型辅助性T细胞的活性，但不抑制记忆性辅助性T细胞的活性，并且这种活性受到与12号染色体上免疫球蛋白重链（Igh）基因座连锁的基因的遗传限制。使用在VHCH区域连接处附近有交叉的Igh重组品系BAB.14，证明调节Igh限制的基因定位于VH基因的端粒。Igh连锁限制调节A4.10 +调节性T细胞与处女型T细胞而非B细胞的相互作用。然而，A4.10 +调节性T细胞并不直接作用于Lyt-2 -辅助性T细胞，而是需要Lyt-2 +细胞的存在才能发挥抑制作用。由GAT致敏的A4.10 +调节性T细胞介导的抑制作用还需要Lyt-2 -和Lyt-2 + T细胞在Igh连锁基因处具有同基因性。这些结果表明A4.10 +调节性T细胞是诱导性调节性T细胞，其激活Lyt-2 +效应性调节性T细胞，从而阻止原发性GAT特异性辅助性T细胞的活性。A4.10 +诱导性调节性T细胞与效应性调节性T细胞之间的相互作用和/或效应性调节性T细胞与其靶细胞之间的相互作用受到与Igh恒定区连锁的基因的限制。
