Romball C G, Weigle W O
Department of Immunology, Scripps Research Institute, La Jolla, California 92037.
J Exp Med. 1993 Nov 1;178(5):1637-44. doi: 10.1084/jem.178.5.1637.
The induction of tolerance in mice to preparations of deaggregated human gamma globulin (DHGG) results in in vitro antigen-specific unresponsiveness in CD4+ T cells as well as in both the T helper 1 (Th1) and Th2-like subpopulations. Whereas both CD45RB(hi) and CD45RB(lo) cells from lymph nodes of HGG/complete Freund's adjuvant-immunized mice (control) proliferated in vitro to HGG, both subpopulations from mice previously tolerized with DHGG failed to respond. Furthermore, CD4+ T cells from control, but not from DHGG-injected mice, secreted high levels of interleukin 2 (IL-2) after in vitro stimulation with HGG. Although significant levels of IL-4 in supernatants of control CD4+ cells stimulated with HGG were detected in some, but not all, experiments, significant levels of IL-4 were never detected in supernatants of HGG-stimulated tolerant CD4+ cells. The demonstration that serum IgG1 anti-HGG is preferentially produced in a few tolerant mice that exhibit a leaky tolerant state suggests that tolerance induction may be more difficult to induce in IL-4- than in IL-2-producing cells.
诱导小鼠对解聚的人γ球蛋白（DHGG）制剂产生耐受性，会导致CD4 + T细胞以及T辅助1（Th1）和Th2样亚群出现体外抗原特异性无反应性。来自HGG/完全弗氏佐剂免疫小鼠（对照）淋巴结的CD45RB(hi)和CD45RB(lo)细胞在体外均能对HGG发生增殖反应，而先前用DHGG诱导耐受的小鼠的这两个亚群均无反应。此外，用HGG进行体外刺激后，对照小鼠而非注射DHGG小鼠的CD4 + T细胞分泌高水平的白细胞介素2（IL-2）。尽管在部分（而非全部）实验中检测到用HGG刺激的对照CD4 +细胞的上清液中有显著水平的IL-4，但在用HGG刺激的耐受CD4 +细胞的上清液中从未检测到显著水平的IL-4。少数呈现渗漏耐受状态的耐受小鼠优先产生血清IgG1抗HGG，这一现象表明，与产生IL-2的细胞相比，诱导IL-4产生细胞产生耐受性可能更困难。
