Liew F Y, Hodson K, Lelchuk R
Department of Experimental Immunobiology, Wellcome Research Laboratories, Beckenham, Kent, United Kingdom.
J Immunol. 1987 Nov 1;139(9):3112-7.
In previous studies, we reported that mice immunized i.v. with lethally irradiated Leishmania major promastigotes developed substantial resistance to a subsequent L. major infection. However, such protection could be totally suppressed by prior s.c. injection with the same antigens. Both the protective immunity and the inhibition of its induction could be adoptively transferred with specific Lyt-2- T cells. Here, we present evidence showing that protection and disease promotion resulting from i.v. or s.c. immunization, respectively, are mediated by functionally distinct subsets of T cells. In a series of titration experiments, it was found that freshly isolated T cells derived from prophylactically i.v. immunized BALB/c mice were either protective (greater than 10(7) cells/recipient) or ineffective (less than 10(7) cells/recipient). No exacerbation of disease was observed at any dose. Conversely, T cells from mice immunized s.c. either accelerated disease development and inhibited protective immunization (greater than 10(7) cells/recipient) or had no effect (less than 10(7) cells/recipient). No protection was observed at any dose tested. In mixed transfer experiments, increasing numbers of T cells from s.c. immunized donors progressively inhibited the protective effect of T cells from i.v. immunized donors. Supernatant of T cell cultures from protectively immunized donors contained substantial macrophage-activating factor whereas such activity was not detectable in the supernatant of T cell culture from s.c. immunized donors. Analysis by flow cytometry showed that the spleen and lymph nodes of normal, i.v., or s.c. immunized BALB/c mice contained similar ratios of L3T4+ cells and Lyt-2+ cells.
在先前的研究中，我们报道静脉注射经致死剂量照射的硕大利什曼原虫前鞭毛体免疫的小鼠，对随后的硕大利什曼原虫感染产生了显著抗性。然而，这种保护作用可被预先皮下注射相同抗原完全抑制。保护性免疫及其诱导的抑制作用均可通过特异性Lyt-2⁺ T细胞进行过继转移。在此，我们提供证据表明，分别由静脉注射或皮下注射免疫所导致的保护作用和疾病促进作用，是由功能不同的T细胞亚群介导的。在一系列滴定实验中，发现从预防性静脉注射免疫的BALB/c小鼠中新鲜分离的T细胞，要么具有保护作用（大于10⁷个细胞/受体），要么无效（小于10⁷个细胞/受体）。在任何剂量下均未观察到疾病加重。相反，来自皮下免疫小鼠的T细胞，要么加速疾病发展并抑制保护性免疫（大于10⁷个细胞/受体），要么无作用（小于10⁷个细胞/受体）。在任何测试剂量下均未观察到保护作用。在混合转移实验中，来自皮下免疫供体的T细胞数量增加，逐渐抑制了来自静脉注射免疫供体的T细胞的保护作用。来自保护性免疫供体的T细胞培养上清液含有大量巨噬细胞激活因子，而在来自皮下免疫供体的T细胞培养上清液中未检测到这种活性。流式细胞术分析表明，正常、静脉注射或皮下免疫的BALB/c小鼠的脾脏和淋巴结中，L3T4⁺细胞和Lyt-2⁺细胞的比例相似。
