Relationship between IL-2 receptor expression and proliferative responses in lymphocytes from HIV-1 seropositive homosexual men.
Previous studies have shown that exogenous IL-2 does not correct the reduction in phytohaemagglutinin (PHA)-induced proliferation of lymphocytes from HIV-1 infected (HIV+) individuals. We investigated the mechanism of this reduction to determine if reduced expression of the complete IL-2 receptor (IL-2R) was responsible. In a series of experiments, PHA-stimulated lymphocytes from a total of 89 HIV- and 93 HIV+ homosexual men from the Baltimore Multicentre AIDS Cohort Study (MACS) were studied to determine the expression of messages for the alpha and beta subunits of the IL-2R, the binding of 125I-IL-2 to high affinity IL-2R, and the effect of IL-2 on cell proliferation. Compared to HIV- donors, PHA-stimulated lymphocytes from most HIV+ donors demonstrated (i) a reduction in high affinity IL-2R expression that correlated with the reduction in the IL-2-induced proliferative response; and (ii) a reduction in expression of both IL-2R alpha- and beta-chain mRNA which may be responsible for decreased high affinity IL-2R expression. However, lymphocytes from some HIV+ individuals had borderline low IL-2-induced proliferation despite normal or elevated expression of high affinity IL-2R. These results suggest that decreased expression of IL-2R may account, at least in part, for the lower proliferative response of cells from HIV+ donors.
Chopra
R K
RK
Department of Environmental Health Sciences, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, MD 21205.
Raj
N B
NB
Scally
J P
JP
Donnenberg
A D
AD
Adler
W H
WH
Saah
A J
AJ
Margolick
J B
JB
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D006679:HIV Seropositivity / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006716:Homosexuality; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000032:analysis* / Q000235:genetics
D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2