IL-2-induced CD4+ T-cell expansion in HIV-infected patients is associated with long-term decreases in T-cell proliferation.
Administration of interleukin 2 (IL-2) leads to selective and sustained CD4+ T-cell expansions in patients infected with HIV. It has been hypothesized that persistent CD4+ T-cell proliferation is the primary mechanism maintaining these expansions. T-cell proliferation was studied by ex vivo bromodeoxyuridine (BrdU) incorporation and intracellular Ki67 staining in HIV-infected patients treated with antiretroviral therapy (ART) with or without IL-2. In contrast to the tested hypothesis, HIV-infected patients treated with IL-2 had lower CD4+ T-cell proliferation compared to patients treated with ART alone. Independently of viral load changes, administration of IL-2 led to a decrease in basal CD4+ T-cell proliferation. Total numbers of CD4+ T cells with naive and recall, but not effector, memory phenotype were increased. The degree of CD4+ T-cell expansion correlated with the decreases in proliferation and a strong association was seen between these decreases and the expansion of the CD4+/CD25+ subset. Intermittent IL-2 in HIV-infected patients leads to expansions of CD4+/CD25+ T cells with naive and recall memory phenotypes that strongly correlate with decreases in proliferation. These data suggest that decreased T-cell proliferation is central in the CD4+ T-cell expansions induced by IL-2.
Sereti
Irini
I
Clinical and Molecular Retrovirology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. isereti@niaid.nih.gov
Anthony
Kara B
KB
Martinez-Wilson
Hector
H
Lempicki
Richard
R
Adelsberger
Joseph
J
Metcalf
Julia A
JA
Hallahan
Claire W
CW
Follmann
Dean
D
Davey
Richard T
RT
Kovacs
Joseph A
JA
Lane
H Clifford
HC
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D015331:Cohort Studies; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use*; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D019380:Anti-HIV Agents; D007376:Interleukin-2