Chow K P, Battisto J R
Department of Biology, Case Western Reserve University, Cleveland, OH 44106.
J Immunol. 1988 Feb 15;140(4):1005-13.
Down-regulation of the development of CTL has been studied in mice both in vivo and in vitro. To generate CTL to hapten-altered self Ag in vivo, an immunization protocol has been used in which the host's Th cells are stimulated by a minor locus histocompatibility Ag (Mlsd) and its precursor CTL are activated by trinitrophenylated syngeneic spleen cells. Injecting the H-2 compatible Mls-disparate spleen cells along with the TNP-coupled self cells into the hind paws causes TNP-self specific CTL to appear in popliteal lymph nodes within 5 days. We have previously reported that inducing Ts cells by i.v. injecting Mlsd-bearing cells prevents in vivo generation of TNP-self specific CTL after immunization in this way. Here the induced Ts cell as well as the mechanism by which it functions have been further examined. The suppression was seen to extend to allogeneic as well as TNP-self Ag, provided the Mlsd-tolerized animal was reexposed to Mlsd-bearing cells at the time of immunization for CTL. By transferring the Mlsd-induced suppression adoptively we have learned that the splenic suppressor cell bears Thy-1.2 as well as Lyt-1.1 Ag and inhibits the generation of CTL at the afferent limb. In addition, Mlsd-induced PEC of Mlsd-tolerized mice, but not of normal mice, mediated suppression of development of CTL in vivo. The active cells within the tolerized PEC have been identified as T cells and macrophages (M phi). Furthermore, PEC from mice tolerized to Mlsd suppressed generation of CTL directed toward TNP-self targets in vitro. T cells and M phi separated from PEC of Mlsd-tolerized mice achieved suppression best in culture when present together. In addition, Lyt-1+ splenic cells from tolerized but not normal mice cooperated to down-regulate CTL generation in vitro with peritoneal M phi from either tolerized or normal mice. Supernatants of 24- to 72-h cultures of PEC from tolerized mice were suppressive of CTL generation when incorporated at 40 to 50% of culture volume. Supernatants of T cells from tolerized PEC or spleen were suppressive in culture only when M phi from normal mice were also present. To achieve suppression dialyzed supernatants of M phi from tolerized mice could replace the M phi.(ABSTRACT TRUNCATED AT 400 WORDS)
在小鼠体内和体外均对细胞毒性T淋巴细胞（CTL）发育的下调进行了研究。为了在体内产生对半抗原改变的自身抗原的CTL，采用了一种免疫方案，即宿主的辅助性T细胞（Th细胞）由次要组织相容性抗原（Mlsd）刺激，其前体CTL由三硝基苯化的同基因脾细胞激活。将H-2相容但Mls不同的脾细胞与TNP偶联的自身细胞一起注射到后爪，会使TNP-自身特异性CTL在5天内在腘窝淋巴结中出现。我们之前报道过，通过静脉注射携带Mlsd的细胞诱导调节性T细胞（Ts细胞），可防止以这种方式免疫后体内产生TNP-自身特异性CTL。在此，对诱导的Ts细胞及其发挥作用的机制进行了进一步研究。结果发现，只要在免疫CTL时将耐受Mlsd的动物重新暴露于携带Mlsd的细胞，这种抑制作用就会扩展到同种异体抗原以及TNP-自身抗原。通过过继转移Mlsd诱导的抑制作用，我们了解到脾抑制细胞带有Thy-1.2以及Lyt-1.1抗原，并在传入阶段抑制CTL的产生。此外，耐受Mlsd的小鼠的Mlsd诱导的腹腔渗出细胞（PEC），而非正常小鼠的PEC，在体内介导了CTL发育的抑制。耐受PEC内的活性细胞已被鉴定为T细胞和巨噬细胞（M phi）。此外，来自耐受Mlsd的小鼠的PEC在体外抑制了针对TNP-自身靶标的CTL的产生。当一起存在时，从耐受Mlsd的小鼠的PEC中分离出的T细胞和M phi在培养中实现了最佳抑制效果。此外，来自耐受但非正常小鼠的Lyt-1 +脾细胞与来自耐受或正常小鼠的腹膜M phi协同作用，在体外下调CTL的产生。当以40%至50%的培养体积加入时，来自耐受小鼠的PEC的24至72小时培养物的上清液对CTL的产生具有抑制作用。仅当也存在来自正常小鼠的M phi时，来自耐受PEC或脾脏的T细胞的上清液在培养中才具有抑制作用。为了实现抑制，来自耐受小鼠的M phi的透析上清液可以替代M phi。（摘要截断于400字）
