SUPPRESSED PROLIFERATIVE RESPONSE AND INTERLEUKIN-2 PRODUCTION IN HISPANIC HIV-CELL SUBSETS( AND AIDS T)

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 C on A together with phorbol eater (PMA) or anti-CD28 coactivation. Like wise, the proliferative response of CD4(+) T-cells was suppressed, fro m a mean of 24.6% (HIV+) to 59.1% (AIDS) for PMA with activators OKT3 (anti-CD3), Con A, enteroxin B or pokweed mitogen, and 20.2% (HIV+) to 77.8% (AIDS) with anti-CD28 co-activation. Similar degrees of suppres sion were found with the CD8(+) T-cells except for a much greater supp ression at the HIV+ stage with anti-CD28 (57.7%), approximately 2.5 ti mes higher than for PMA coactivation. However, when proliferation was induced by the two coactivators combined (PMA plus anti-CD28), much le ss suppression was observed: 8.5% (HIV+) to 19.0% (AIDS) for CD4(+) ce lls and 8.2% to 26.5%, respectively, for CD8(+) cells. The data sugges t that during HIV infection the CD28 pathway becomes most defective, b ut can be bypassed to some extent by the less-impaired PMA pathway. Th e IL-2 (+PMA) signal in HIV+ and AIDS cells was also significally less suppressed suggesting that the disregulation in HIV infection is more prominent prior to the IL-2 stage of the mitogenic pathway. It is rem arkable that the CD4(+) and CD8(+) T-cells at both the HIV+ and AIDS s tages generally show the same degree of suppression with all the vario us activators and coactivators used. These data suggest that the mecha nism of suppression, whether due to a change in cell phenotype such as T(H)1 to T(H)2, or from an intrinsic inhibitory mechanism, is similar and equally expressed in the two T-cell subsets, and independent of t he factors that lead to CD4(+) T-cell depletion. The data also suggest that neither viral protein gp 120 nor interleukin-10 (IL-10), which w ould affect CD4(+) cells preferentially to the CD8(+) cells, appear to be accountable factors. A putative HIV superantigen is also unlikely in view of the similar degree of suppression to enterotoxin B as other activators for AIDS and HIV+ subsets in both CD4(+) and CD8(+) T-cell s.