Vassena Lia, Proschan Michael, Fauci Anthony S, Lusso Paolo
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Proc Natl Acad Sci U S A. 2007 Feb 13;104(7):2355-60. doi: 10.1073/pnas.0610775104. Epub 2007 Feb 6.
Apoptosis has been suggested as one of the major mechanisms of CD4+ T cell depletion during the course of HIV type 1 (HIV-1) infection. Here, we show that interleukin 7 (IL-7), a nonredundant cytokine that plays essential roles in the generation and homeostasis of the T cell compartment of the immune system, exerts strong antiapoptotic effects ex vivo on both CD4+ and CD8+ T cells derived from HIV-1-infected subjects. The level of IL-7-mediated reduction of apoptosis was inversely correlated with the number of circulating CD4+ T cells, indicating a higher sensitivity to IL-7 effects in patients with more advanced disease. The antiapoptotic effect of IL-7 was uncoupled from the induction of cellular proliferation or endogenous HIV-1 replication. These results provide a further rationale for consideration of IL-7 as an agent of immune reconstitution in HIV-1 infection.
细胞凋亡被认为是1型人类免疫缺陷病毒（HIV-1）感染过程中CD4 + T细胞耗竭的主要机制之一。在此，我们表明白细胞介素7（IL-7）是一种在免疫系统T细胞区室的产生和稳态中起重要作用的非冗余细胞因子，它在体外对来自HIV-1感染受试者的CD4 +和CD8 + T细胞均具有强大的抗凋亡作用。IL-7介导的细胞凋亡减少水平与循环CD4 + T细胞数量呈负相关，表明病情更严重的患者对IL-7作用的敏感性更高。IL-7的抗凋亡作用与细胞增殖诱导或内源性HIV-1复制无关。这些结果为将IL-7作为HIV-1感染免疫重建药物的考虑提供了进一步的理论依据。
