Holaday B, Sadick M D, Pearson R D
Department of Microbiology, University of Virginia School of Medicine, Charlottesville 22908.
J Immunol. 1988 Sep 15;141(6):2132-7.
BALB/cJ mice, which are homozygous for Lshs on chromosone 1, are genetically susceptible to Leishmania donovani (S3), but spontaneously reduce their parasite burdens late in the course of infection. Spleens from chronically infected mice (5 to 8 mo) were found to have T cells that responded to leishmanial Ag by proliferating and secreting immune IFN. An IFN-secreting T cell line derived from the spleen of a chronically infected mouse, after boosting with leishmanial Ag and treatment with Pentostam to kill residual parasites, was able to activate macrophages to kill amastigotes in vitro. Furthermore, after adoptive transfer of this cell line, naive BALB/cJ mice challenged with amastigotes demonstrated a 42-fold reduction in parasite burden compared to controls. Four of five clones derived from the protective T cell line secreted IFN and proliferated between days 7 and 14 after Ag stimulation. All clones were Ly1+2-, L3T4+. Another T cell line, which had Ly1+2-, L3T4+ phenotype, was derived from the lymph nodes of s.c. immunized, uninfected mice. It multipled but never produced IFN in response to leishmanial Ag and failed to protect macrophages against L. donovani infection in vitro or in vivo. This nonprotective T cell line and the fifth clone from the protective line, which also did not secrete IFN, proliferated between days 2 and 7 after Ag stimulation. In summary, leishmania-responsive helper/inducer T cells, which produced IFN but were slow to proliferate in response to Ag in vitro and which were able to activate macrophages to reduce amastigotes in vitro and in vivo, are present in chronically infected BALB/cJ mice and may mediate the decrease in parasite burden during chronic infection.
BALB/cJ小鼠在1号染色体上为Lshs纯合子，对杜氏利什曼原虫具有遗传易感性（S3），但在感染后期会自发降低其寄生虫负荷。发现慢性感染小鼠（5至8个月）的脾脏中有T细胞，这些T细胞通过增殖和分泌免疫干扰素对利什曼原虫抗原作出反应。从慢性感染小鼠脾脏中获得的一个分泌干扰素的T细胞系，在用利什曼原虫抗原刺激并用喷他脒处理以杀死残留寄生虫后，能够在体外激活巨噬细胞以杀死无鞭毛体。此外，在过继转移该细胞系后，用无鞭毛体攻击的未感染BALB/cJ小鼠与对照组相比，寄生虫负荷降低了42倍。从保护性T细胞系衍生的五个克隆中有四个在抗原刺激后7至14天之间分泌干扰素并增殖。所有克隆均为Ly1 + 2 -、L3T4 +。另一个具有Ly1 + 2 -、L3T4 +表型的T细胞系来自皮下免疫的未感染小鼠的淋巴结。它能够增殖，但对利什曼原虫抗原无反应，不产生干扰素，并且在体外或体内均不能保护巨噬细胞免受杜氏利什曼原虫感染。这个非保护性T细胞系和保护性细胞系的第五个克隆也不分泌干扰素，在抗原刺激后2至7天之间增殖。总之，在慢性感染的BALB/cJ小鼠中存在对利什曼原虫有反应的辅助/诱导性T细胞，它们产生干扰素，但在体外对抗原反应增殖缓慢，并且能够在体外和体内激活巨噬细胞以减少无鞭毛体，可能介导慢性感染期间寄生虫负荷的降低。
