title: Lenalidomide enhancement of human T cell functions in human immunodeficiency virus (HIV)-infected and HIV-negative CD4 T lymphocytopenic patients.
abstract: 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.
authors: Department of Medicine, University of California and San Francisco General Hospital, CA, USA.
authors: H
authors: H
authors: Lim
authors: L
authors: L
authors: Kane
authors: J B
authors: JB
authors: Schwartz
authors: C S
authors: CS
authors: Hesdorffer
authors: S G
authors: SG
authors: Deeks
authors: N
authors: N
authors: Greig
authors: L
authors: L
authors: Ferrucci
authors: E J
authors: EJ
authors: Goetzl
mesh_terms: D000328:Adult; D016516:CD4-CD8 Ratio; D002633:Chemotaxis / Q000187:drug effects / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018344:T-Lymphocytopenia, Idiopathic CD4-Positive / Q000276:immunology* / Q000821:virology; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D007376:Interleukin-2; D013792:Thalidomide; D000077269:Lenalidomide