Restoration of HIV-specific cell-mediated immune responses by interleukin-12 in vitro.
Peripheral blood mononuclear cells (PBMCs) from many asymptomatic individuals infected with human immunodeficiency virus-type 1 (HIV) are unresponsive as measured by in vitro T cell proliferation and interleukin-2 (IL-2) production to influenza virus and synthetic peptides of HIV envelope (Env). Strong influenza virus- and Env-stimulated IL-2 responses and T cell proliferation were restored when cultures were stimulated in the presence of IL-12. Interferon-gamma production by PBMCs from HIV seropositive (HIV+) patients was also restored with IL-12. Furthermore, in vitro antigen-specific production of IL-2 and proliferation of PBMCs from HIV- donors were suppressed by antibody to IL-12, but were not enhanced by addition of exogenous IL-12. Thus, IL-12 may be limiting in PBMCs from HIV+ but not HIV- individuals. These findings demonstrate that IL-12 can restore HIV-specific cell-mediated immunity in vitro in HIV-infected individuals and suggest a potential use of IL-12 in augmenting the diminished immunologic functions associated with HIV infection.
Clerici
M
M
Experimental Immunology Branch, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892.
Lucey
D R
DR
Berzofsky
J A
JA
Pinto
L A
LA
Wynn
T A
TA
Blatt
S P
SP
Dolan
M J
MJ
Hendrix
C W
CW
Wolf
S F
SF
Shearer
G M
GM
D002478:Cells, Cultured; D015686:Gene Products, env / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D009980:Influenza A virus / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D007378:Interleukins / Q000276:immunology / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation; D010835:Phytohemagglutinins / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D015686:Gene Products, env; D007376:Interleukin-2; D007378:Interleukins; D010835:Phytohemagglutinins; D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma