Suppressed proliferative response and interleukin-2 production in hispanic HIV+ and AIDS T-cell subsets.
We find that interleukin-2 (IL-2) production is severely depressed (80-90%) in AIDS T-cells (CD4+ or CD8+) stimulated with anti-CD3 or Con A together with phorbol ester (PMA) or anti-CD28 coactivation. Likewise, the proliferative response of CD4+ T-cells was suppressed, from a mean of 24.6% (HIV+) to 59.1% (AIDS) for PMA with activators OKT3 (anti-CD3), Con A, enterotoxin B or pokeweed mitogen, and 20.2% (HIV+) to 77.8% (AIDS) with anti-CD28 co-activation. Similar degrees of suppression were found with the CD8+ T-cells except for a much greater suppression at the HIV+ stage with anti-CD28 (57.7%), approximately 2.5 times higher than for PMA coactivation. However, when proliferation was induced by the two coactivators combined (PMA plus anti-CD28), much less suppression was observed: 8.5% (HIV+) to 19.0% (AIDS) for CD4+ cells and 8.2% to 26.5%, respectively, for CD8+ cells. The data suggest that during HIV infection the CD28 pathway becomes most defective, but can be bypassed to some extent by the less-impaired PMA pathway. The IL-2 (+PMA) signal in HIV+ and AIDS cells was also significantly less suppressed suggesting that the disregulation in HIV infection is more prominent prior to the IL-2 stage of the mitogenic pathway. It is remarkable that the CD4+ and CD8+ T-cells at both the HIV+ and AIDS stages generally show the same degree of suppression with all the various activators and coactivators used.(ABSTRACT TRUNCATED AT 250 WORDS)
Eylar
E H
EH
Department of Biochemistry, Ponce School of Medicine 00732, Puerto Rico.
Báez
I
I
Vázquez
A
A
Colón-Martínez
S L
SL
Yamamura
Y
Y
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology; D000328:Adult; D018106:CD28 Antigens / Q000502:physiology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003208:Concanavalin A / Q000494:pharmacology; D004768:Enterotoxins / Q000494:pharmacology; D015658:HIV Infections / Q000276:immunology*; D006630:Hispanic or Latino; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D011043:Pokeweed Mitogens / Q000494:pharmacology; D012720:Severity of Illness Index; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D018106:CD28 Antigens; D004768:Enterotoxins; D007376:Interleukin-2; D011043:Pokeweed Mitogens; D003208:Concanavalin A; C031818:enterotoxin B, staphylococcal; D013755:Tetradecanoylphorbol Acetate