Liew F Y, Singleton A, Cillari E, Howard J G
J Immunol. 1985 Sep;135(3):2102-7.
The responsiveness of BALB/c mice to protective i.v. immunization with 150,000-rad irradiated or heat-killed Leishmania major promastigotes can be totally suppressed by prior subcutaneous (s.c.) injection of the same "vaccine." Induction of this effect is leishmania specific for although prevention of protection against L. major infection can be obtained with either homologous or Leishmania donovani promastigotes, it does not follow s.c. administration of an immunogenic Trypanosoma cruzi epimastigote preparation. Multiple s.c. injections of irradiated L. major promastigotes do not inhibit the subsequent antibody response of any major isotype to i.v. immunization, but rather induce some priming. The same s.c. injections induced delayed-type hypersensitivity (DTH) reactivity that could be transferred locally or systemically, although it was weaker than in mice with cured infections. Parallel cell-mediated immunity (CMI) responses were also reflected in vitro in specific lymphocyte transformation assays. Despite this evidence of a DTH/helper type of T cell response, transfer of 5 X 10(7) viable T cell-enriched spleen cells from 4 X s.c. immunized donors to normal recipients completely abrogated the protective response to i.v. immunization. Conversely, T cell-depleted (anti-Thy-1.2 + C treated) cells were without effect. The inhibitory T cells were defined by monoclonal antibody pretreatment as possessing an Lyt-1+2-,L3T4+ phenotype. T cells from s.c. immunized donors were also shown, by mixed transfer experiments, to counteract completely the protective effect of T cells from i.v. immunized donors in 550-rad irradiated recipients. They were as potent as suppressor T cells from donors with progressive disease both in this capacity and in abrogating the prophylactic effect of sublethal irradiation itself. The similarities and differences between suppressor and immune effector T cells induced by s.c. or i.v. immunization and those arising in response to leishmanial infection itself are discussed.
BALB/c小鼠对经150,000拉德辐照或热灭活的硕大利什曼原虫前鞭毛体进行静脉免疫的保护性反应，可被预先皮下注射相同的“疫苗”完全抑制。这种效应的诱导具有利什曼原虫特异性，因为尽管用同源或杜氏利什曼原虫前鞭毛体均可预防硕大利什曼原虫感染，但皮下注射免疫原性克氏锥虫上鞭毛体制剂却不会产生这种效应。多次皮下注射辐照的硕大利什曼原虫前鞭毛体不会抑制随后对静脉免疫的任何主要同种型抗体反应，反而会诱导某种启动作用。相同的皮下注射可诱导迟发型超敏反应（DTH），该反应可局部或全身转移，尽管其比感染已治愈的小鼠中的反应弱。在特异性淋巴细胞转化试验中，体外也反映出平行的细胞介导免疫（CMI）反应。尽管有这种DTH/辅助型T细胞反应的证据，但将来自经4次皮下免疫的供体的5×10⁷个富含活T细胞的脾细胞转移至正常受体，却完全消除了对静脉免疫的保护性反应。相反，T细胞耗竭（抗Thy-1.2 + C处理）的细胞则无作用。通过单克隆抗体预处理确定，抑制性T细胞具有Lyt-1⁺2⁻、L3T4⁺表型。通过混合转移实验还表明，来自皮下免疫供体的T细胞可完全抵消来自静脉免疫供体的T细胞对550拉德辐照受体的保护作用。它们在这种能力以及消除亚致死性辐照本身的预防作用方面，与来自患有进行性疾病的供体的抑制性T细胞一样有效。本文讨论了皮下或静脉免疫诱导的抑制性T细胞与免疫效应T细胞之间以及与利什曼原虫感染本身所产生的抑制性T细胞与免疫效应T细胞之间的异同。
