Lenalidomide enhancement of human T cell functions in human immunodeficiency virus (HIV)-infected and HIV-negative CD4 T lymphocytopenic patients

被引：4

作者：

Lim, H. ^{[1
,2
]}

Kane, L. ^{[1
,2
,3
]}

Schwartz, J. B. ^{[1
,2
,3
,4
]}

Hesdorffer, C. S. ^{[5
]}

Deeks, S. G. ^{[1
,2
]}

Greig, N. ^{[5
]}

Ferrucci, L. ^{[5
]}

Goetzl, E. J. ^{[1
,2
,3
,5
]}

机构：

[1] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA

[2] Univ Calif San Francisco, San Francisco Gen Hosp, San Francisco, CA 94143 USA

[3] Univ Calif San Francisco, Jewish Home San Francisco, Geriatr Res Ctr, San Francisco, CA 94143 USA

[4] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA

[5] NIA, Baltimore, MD 21224 USA

来源：

CLINICAL AND EXPERIMENTAL IMMUNOLOGY | 2012年 / 169卷 / 02期

关键词：

AIDS; chemotaxis; cytokines; immunopharmacology; T lymphocytes; AGE-RELATED COMORBIDITIES; FUNCTION IN-VITRO; HOMOSEXUAL-MEN; MORTALITY; INFLAMMATION; ATHEROSCLEROSIS; PROGRESSION; INFECTION; CHEMOKINE; CYTOKINE;

D O I：

10.1111/j.1365-2249.2012.04603.x

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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)-?, by T cells of middle-aged HIV-infected men was significantly lower than that for controls and was increased significantly by 101000 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-?. Significant enhancement of chemotaxis to S1P and CCL21was induced by 1001000 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-?. Lenalidomide at 301000 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-? 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.

引用

页码：182 / 189

页数：8

共 32 条

[1] Old age and anti-cytomegalovirus immunity are associated with altered T-cell reconstitution in HIV-1-infected patients [J].