Induction of prolonged survival of CD4+ T lymphocytes by intermittent IL-2 therapy in HIV-infected patients.
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.
Kovacs
Joseph A
JA
Critical Care Medicine Department, Warren G. Magnuson Clinical Center, NIH, Bethesda, Maryland, USA. jkovacs@niaid.nih.gov
Lempicki
Richard A
RA
Sidorov
Igor A
IA
Adelsberger
Joseph W
JW
Sereti
Irini
I
Sachau
William
W
Kelly
Grace
G
Metcalf
Julia A
JA
Davey
Richard T
RT
Falloon
Judith
J
Polis
Michael A
MA
Tavel
Jorge
J
Stevens
Randy
R
Lambert
Laurie
L
Hosack
Douglas A
DA
Bosche
Marjorie
M
Issaq
Haleem J
HJ
Fox
Stephen D
SD
Leitman
Susan
S
Baseler
Michael W
MW
Masur
Henry
H
Di Mascio
Michele
M
Dimitrov
Dimiter S
DS
Lane
H Clifford
HC
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
D007376:Interleukin-2; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D017493:Leukocyte Common Antigens