title: Induction of prolonged survival of CD4+ T lymphocytes by intermittent IL-2 therapy in HIV-infected patients.
abstract: HIV infection leads to decreases in the number of CD4 T lymphocytes and an increased risk for opportunistic infections and neoplasms. The administration of intermittent cycles of IL-2 to HIV-infected patients can lead to profound increases (often greater than 100%) in CD4 cell number and percentage. Using in vivo labeling with 2H-glucose and BrdU, we have been able to demonstrate that, although therapy with IL-2 leads to high levels of proliferation of CD4 as well as CD8 lymphocytes, it is a remarkable preferential increase in survival of CD4 cells (with half-lives that can exceed 3 years) that is critical to the sustained expansion of these cells. This increased survival was time-dependent: the median half-life, as determined by semiempirical modeling, of labeled CD4 cells in 6 patients increased from 1.7 weeks following an early IL-2 cycle to 28.7 weeks following a later cycle, while CD8 cells showed no change in the median half-life. Examination of lymphocyte subsets demonstrated that phenotypically naive (CD27+CD45RO-) as well as central memory (CD27+CD45RO+) CD4 cells were preferentially expanded, suggesting that IL-2 can help maintain cells important for host defense against new antigens as well as for long-term memory to opportunistic pathogens.
authors: Critical Care Medicine Department, Warren G. Magnuson Clinical Center, NIH, Bethesda, Maryland, USA. jkovacs@niaid.nih.gov
authors: Joseph A
authors: JA
authors: Kovacs
authors: Richard A
authors: RA
authors: Lempicki
authors: Igor A
authors: IA
authors: Sidorov
authors: Joseph W
authors: JW
authors: Adelsberger
authors: Irini
authors: I
authors: Sereti
authors: William
authors: W
authors: Sachau
authors: Grace
authors: G
authors: Kelly
authors: Julia A
authors: JA
authors: Metcalf
authors: Richard T
authors: RT
authors: Davey
authors: Judith
authors: J
authors: Falloon
authors: Michael A
authors: MA
authors: Polis
authors: Jorge
authors: J
authors: Tavel
authors: Randy
authors: R
authors: Stevens
authors: Laurie
authors: L
authors: Lambert
authors: Douglas A
authors: DA
authors: Hosack
authors: Marjorie
authors: M
authors: Bosche
authors: Haleem J
authors: HJ
authors: Issaq
authors: Stephen D
authors: SD
authors: Fox
authors: Susan
authors: S
authors: Leitman
authors: Michael W
authors: MW
authors: Baseler
authors: Henry
authors: H
authors: Masur
authors: Michele
authors: M
authors: Di Mascio
authors: Dimiter S
authors: DS
authors: Dimitrov
authors: H Clifford
authors: HC
authors: Lane
mesh_terms: D000328:Adult; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects; D007376:Interleukin-2 / Q000008:administration & dosage*; D017493:Leukocyte Common Antigens / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009894:Opportunistic Infections / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000821:virology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology
chemical_list: D007376:Interleukin-2; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D017493:Leukocyte Common Antigens