Effects of cytokines on HIV-1 production by thymocytes.
The thymus is essential for normal T cell development and is particularly active during fetal and postnatal life. Here we describe in vitro studies of HIV-infected thymocytes cultured with cytokines normally produced in the thymus. Virus expression was determined by measuring p24 antigen levels in the culture supernatants. Addition of IL-2+IL-4 and IL-4+IL-7 to the HIV-infected cultures of both fetal and postnatal thymocytes resulted in various levels of synergistic expression of p24 antigen. When differences in phenotype between HIV-infected and non-infected (sham-treated) cultures from the same specimen were evaluated, there was a decrease in the percentages and absolute numbers of CD4-bearing cells in HIV-infected thymocytes cultured with IL-2+IL-4. Studies were done to determine if synergy in HIV expression was mediated by activation, proliferation or induction or suppression of other cytokines. We found a higher percentage of activated CD4+CD8+/high cells in thymocytes cultured with IL-2+IL-4 and IL-4+IL-7 than in thymocytes cultured with IL-2+IL-7. Proliferation was higher in thymocytes cultured with cytokine combinations but did not correlate with those conditions showing synergy. IL-4 reduced IFN-gamma production by thymocytes cultured with IL-2 in both HIV-infected and non-infected thymocytes. In addition, exogenous IFN-gamma decreased p24 expression by HIV-infected thymocytes when cultured with IL-4 alone, with IL-2+IL-4 or IL-4+IL-7. These results suggest that suppression of IFN-gamma by IL-4 may combine with cell activation and proliferation to produce synergy of virus expression observed with IL-2+IL-4 and IL-4+IL-7.
Department of Pediatrics, UCLA School of Medicine, USA.
C H
CH
Uittenbogaart
D J
DJ
Anisman
J A
JA
Zack
A
A
Economides
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I
Schmid
E F
EF
Hays
D000375:Aging / Q000276:immunology; D002478:Cells, Cultured; D002648:Child; D016207:Cytokines / Q000494:pharmacology*; D003609:Dactinomycin / Q000031:analogs & derivatives / Q000494:pharmacology; D005314:Embryonic and Fetal Development / Q000276:immunology; D005333:Fetus; D005865:Gestational Age; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D016655:HIV Core Protein p24 / Q000032:analysis / Q000096:biosynthesis; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology*; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology*
D016207:Cytokines; D016655:HIV Core Protein p24; D007375:Interleukin-1; D015850:Interleukin-6; D015851:Interleukin-7; D007378:Interleukins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D015847:Interleukin-4; C025942:7-aminoactinomycin D; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor