Changes in interleukin-2 and interleukin-4 production in asymptomatic, human immunodeficiency virus-seropositive individuals.
Infection with HIV results in an incremental loss of T helper cell (TH) function, which can occur years before CD4 cell numbers are critically reduced and AIDS is diagnosed. All TH function is not affected, however, because B cell activation and hypergammaglobulinema are also characteristic of this period. Recently, in a murine model of AIDS an early loss in production of the CD4 cytokines IL-2 and IFN-gamma was correlated with an increase in the B cell stimulatory cytokines IL-4, IL-5, and IL-10. We therefore assessed the production of IL-4 generated by PBL from HIV-seropositive (HIV+) individuals who did not have AIDS, yet who exhibited different TH functional categories based on their IL-2 production profiles. We observed that the decreases in recall antigen-stimulated IL-2 production were accompanied by an increase in IL-4 production. The loss of recall antigen-stimulated responses in HIV+ individuals could be reversed in vitro by anti-IL-4 antibody. Our results suggest that the TH functions assessed by IL-4 production replace the normally dominant TH function of antigen-stimulated IL-2 production in the progression toward AIDS, and raise the possibility of cytokine cross-regulation in AIDS therapy.
Clerici
M
M
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Hakim
F T
FT
Venzon
D J
DJ
Blatt
S
S
Hendrix
C W
CW
Wynn
T A
TA
Shearer
G M
GM
D016375:Antisense Elements (Genetics); D001483:Base Sequence; D016516:CD4-CD8 Ratio; D002478:Cells, Cultured; D006678:HIV; D015483:HIV Antibodies / Q000097:blood; D006679:HIV Seropositivity / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000097:blood; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology*; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D012016:Reference Values; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D016375:Antisense Elements (Genetics); D015483:HIV Antibodies; D007376:Interleukin-2; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D015847:Interleukin-4