Clinical Sciences Division, University of Toronto, Toronto, Canada.
PLoS One. 2007 Mar 21;2(3):e300. doi: 10.1371/journal.pone.0000300.
HIV specific T cells are putatively anergic in vivo. IL-2, a member of a class of cytokines that binds to receptors containing the common gamma chain (gammac) has been shown to reverse anergy. We examined the role of gammac cytokines in reversing HIV specific T cell anergy.
PBMC from untreated HIV-infected individuals were briefly exposed to a panel of gammac cytokines, and frequencies of gag specific T cells were enumerated by intracellular IFN-gamma flow cytometry.
Of the gammac cytokines, brief exposure to IL-2, IL-15, or combined IL-15/IL-7 significantly enhanced (range 2-7 fold) the CD4(+) and CD8(+) T cell IFN-gamma responses to HIV gag, with IL-15 giving the greatest enhancement. The effects of cytokines were not due to enhanced proliferation of pre-existing antigen specific cells, but were due to a combination of enhanced cytokine production from antigen specific T cells plus activation of non-epitope specific T cells.
These observations support the notion that a significant number of HIV specific T cells are circulating in an anergic state. IL-2, IL-7 and particularly IL-15 as an immune modulator to reverse HIV-1 specific T cell anergy should be investigated, with the caveat that non-specific activation of T cells may also be induced.
HIV 特异性 T 细胞在体内被假定为无反应性的。白细胞介素 2（IL-2）是一类与含有共同γ链（γc）的受体结合的细胞因子，已被证明可以逆转无反应性。我们研究了γc 细胞因子在逆转 HIV 特异性 T 细胞无反应性中的作用。
从未经治疗的 HIV 感染者的 PBMC 中短暂暴露于一组 γc 细胞因子，并通过细胞内 IFN-γ流式细胞术计数 gag 特异性 T 细胞的频率。
在 γc 细胞因子中，短暂暴露于 IL-2、IL-15 或联合 IL-15/IL-7 显著增强（范围 2-7 倍）CD4+和 CD8+T 细胞对 HIV gag 的 IFN-γ反应，其中 IL-15 增强作用最大。细胞因子的作用不是由于预先存在的抗原特异性细胞的增殖增强，而是由于抗原特异性 T 细胞产生增强的细胞因子加上非表位特异性 T 细胞的激活的组合。
这些观察结果支持这样一种观点，即大量 HIV 特异性 T 细胞处于无反应性状态。应该研究 IL-2、IL-7 特别是 IL-15 作为逆转 HIV-1 特异性 T 细胞无反应性的免疫调节剂，但其缺点是可能也会诱导非特异性 T 细胞的激活。
