Immunobiology Program and Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, IA 50011-1250, USA.
Cell Immunol. 2011;270(1):32-9. doi: 10.1016/j.cellimm.2011.03.016. Epub 2011 Apr 9.
C3H mice infected with Leishmania amazonensis develop persistent, localized lesions with high parasite loads. During infection, memory/effector CD44(hi)CD4(+) T cells proliferate and produce IL-2, but do not polarize to a known effector phenotype. Previous studies have demonstrated IL-12 is insufficient to skew these antigen-responsive T cells to a functional Th1 response. To determine the mechanism of this IL-12 unresponsiveness, we used an in vitro assay of repeated antigen activation. Memory/effector CD44(hi)CD4(+) T cells did not increase proliferation in response to either IL-2 or IL-12, although these cytokines upregulated CD25 expression. Neutralization of IL-2 enhanced CD4(+) T cell proliferation in response to IL-12. This cross-regulation of IL-12 responsiveness by IL-2 was confirmed in vivo by treatment with anti-IL-2 antibodies and IL-12 during antigen challenge of previously infected mice. These results suggest that during chronic infection with L. amazonensis, IL-2 plays a dominant, immunosuppressive role independent of identifiable conventional T(reg) cells.
感染莱什曼原虫亚马逊亚种的 C3H 小鼠会发展出持续的、局部的病变，寄生虫负荷很高。在感染过程中，记忆/效应 CD44(hi)CD4(+)T 细胞增殖并产生 IL-2，但不会向已知的效应表型极化。先前的研究表明，IL-12 不足以使这些抗原反应性 T 细胞偏向于功能性 Th1 反应。为了确定这种 IL-12 无反应性的机制，我们使用了重复抗原激活的体外测定。记忆/效应 CD44(hi)CD4(+)T 细胞对 IL-2 或 IL-12 的增殖反应均未增加，尽管这些细胞因子上调了 CD25 的表达。IL-2 的中和增强了 CD4(+)T 细胞对 IL-12 的增殖反应。在先前感染的小鼠进行抗原挑战期间，用抗 IL-2 抗体和 IL-12 治疗，在体内证实了这种 IL-12 反应性的交叉调节。这些结果表明，在慢性感染莱什曼原虫亚马逊亚种时，IL-2 发挥了占主导地位的免疫抑制作用，而与可识别的常规 T(reg)细胞无关。
