Reiner S L, Fowell D J, Moskowitz N H, Swier K, Brown D R, Brown C R, Turck C W, Scott P A, Killeen N, Locksley R M
Department of Medicine, Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, IL 60637, USA.
J Immunol. 1998 Jan 15;160(2):884-9.
Little is known regarding the diversity of the host T cell response that is required to maintain immunologic control of microbial pathogens. Leishmania major persist as obligate intracellular parasites within macrophages of the mammalian host. Immunity is dependent upon activation of MHC class II-restricted T cells to an effector state capable of restricting growth and dissemination of the organisms. We generated alpha-beta Leishmania-specific (ABLE) TCR transgenic mice with MHC class II-restricted T cells that recognized an immunodominant Leishmania Ag designated LACK. Naive T cells from ABLE mice proliferated in vitro after incubation with recombinant LACK or with Leishmania-parasitized macrophages and in vivo after injection into infected mice. Infected ABLE mice controlled Leishmania infection almost as well as wild-type mice despite a drastic reduction in the T cell repertoire. ABLE mice were crossed to mice with disruption of the TCR constant region alpha gene to create animals with a single alpha beta T cell repertoire. Although mice deficient in all alpha beta T cells (TCR-C alpha 0 mice) failed to control L. major, mice with a monoclonal alpha beta T cell repertoire (ABLE TCR-C alpha 0 mice) displayed substantial control. The immune system is capable of remarkable efficiency even when constrained to recognition of a single epitope from a complex organism.
关于维持对微生物病原体免疫控制所需的宿主T细胞反应的多样性，我们了解得很少。硕大利什曼原虫作为专性细胞内寄生虫寄生于哺乳动物宿主的巨噬细胞内。免疫依赖于MHC II类限制性T细胞激活至能够限制病原体生长和传播的效应状态。我们构建了具有MHC II类限制性T细胞的α-β利什曼原虫特异性（ABLE）TCR转基因小鼠，这些T细胞识别一种名为LACK的免疫显性利什曼原虫抗原。与重组LACK或利什曼原虫寄生的巨噬细胞孵育后，ABLE小鼠的初始T细胞在体外增殖，注射到感染小鼠体内后在体内增殖。尽管T细胞库大幅减少，但感染的ABLE小鼠对利什曼原虫感染的控制能力几乎与野生型小鼠相同。将ABLE小鼠与TCR恒定区α基因缺失的小鼠杂交，以培育出具有单一α-β T细胞库的动物。尽管所有α-β T细胞缺陷的小鼠（TCR-Cα0小鼠）无法控制硕大利什曼原虫感染，但具有单克隆α-β T细胞库的小鼠（ABLE TCR-Cα0小鼠）表现出显著的控制能力。即使免疫系统只能识别来自复杂生物体的单个表位，它也能具有非凡的效率。
