Department of Medicine, University of California and San Francisco General Hospital, CA, USA.
Clin Exp Immunol. 2012 Aug;169(2):182-9. doi: 10.1111/j.1365-2249.2012.04603.x.
Suppressed T cell functions in human immunodeficiency virus (HIV) infection were identified and corrected by lenalidomide in middle-aged HIV-infected patients. Chemotaxis of T cells from HIV-infected men (n = 6, mean 43 years) to sphingosine 1-phosphate (S1P) and CCL21 was significantly lower than that of HIV-negative men (n = 6, mean 41 years), and was enhanced significantly up to control levels by 100 and 1000 nM lenalidomide. Generation of interleukin (IL)-2, but not interferon (IFN)-γ, by T cells of middle-aged HIV-infected men was significantly lower than that for controls and was increased significantly by 10-1000 nM lenalidomide up to a maximum of more than 300%. CD4 and CD8 T cells isolated from healthy middle-aged men and reconstituted in vitro at a low CD4 : CD8 ratio typical of HIV infection had depressed chemotaxis to S1P, but not CCL21, and generation of IL-2, but not IFN-γ. Significant enhancement of chemotaxis to S1P and CCL21 was induced by 100-1000 nM lenalidomide only for normal T cells at a low CD4 : CD8 ratio. T cells from HIV-negative middle-aged CD4 T lymphocytopenic patients (n = 3), with a CD4 : CD8 ratio as low as that of HIV-infected patients, had similarly diminished chemotaxis to S1P and CCL21, and depressed generation of IL-2, but not IFN-γ. Lenalidomide at 30-1000 nM significantly enhanced chemotaxis to S1P and IL-2 generation for T cells from HIV-negative CD4 T lymphocytopenic patients as from HIV-infected patients, with less effect on CCL21-elicited chemotaxis and none for IFN-γ generation. Defects in functions of T cells from middle-aged HIV-infected men are partially attributable to CD4 T lymphocytopenia and are corrected by lenalidomide.
来那度胺可纠正中年 HIV 感染者体内被抑制的 T 细胞功能。
HIV 感染男性患者（n = 6，平均年龄 43 岁）的 T 细胞向鞘氨醇 1-磷酸（S1P）和 CCL21 的趋化作用明显低于 HIV 阴性男性（n = 6，平均年龄 41 岁），100 和 1000 nM 来那度胺可显著增强 T 细胞趋化作用，达到对照水平。
与对照组相比，中年 HIV 感染者 T 细胞产生白细胞介素（IL）-2而非干扰素（IFN）-γ的能力明显降低，10-1000 nM 来那度胺可显著增加 T 细胞产生白细胞介素（IL）-2的能力，最大增加超过 300%。
从健康中年男性分离的 CD4 和 CD8 T 细胞在体外以低 CD4：CD8 比例重建，该比例与 HIV 感染时典型的比例相似，表现出对 S1P 的趋化作用降低，但对 CCL21 的趋化作用正常，且产生 IL-2，但不产生 IFN-γ。仅在低 CD4：CD8 比时，100-1000 nM 来那度胺才能显著增强 S1P 和 CCL21 的趋化作用。
HIV 阴性中年 CD4 T 淋巴细胞减少症患者（n = 3）的 CD4：CD8 比值与 HIV 感染者相似，其 S1P 和 CCL21 趋化作用明显降低，IL-2 生成减少，但 IFN-γ 生成不受影响。30-1000 nM 来那度胺可显著增强 HIV 阴性 CD4 T 淋巴细胞减少症患者 T 细胞的 S1P 趋化作用和 IL-2 生成，对 CCL21 诱导的趋化作用影响较小，对 IFN-γ 生成无影响。
中年 HIV 感染者 T 细胞功能缺陷部分归因于 CD4 T 淋巴细胞减少症，可通过来那度胺纠正。
