HIV infection and aging: enhanced Interferon- and Tumor Necrosis Factor-alpha production by the CD8+ CD28- T subset.

Background: T cells from HIV+ and aged individuals show parallels in terms of suppressed proliferative activity and interleukin-2 (I1-2) production and an increased number of CD8+ CD28- T cells. In order to compare cytokine production from T cells from these two states, CD4+ and CD8+ T cells from HIV+ aged, and normal young donors (controls) were monitored for cytokine production by flow cytometry, quantitative PCR and ELISA upon activation by PMA and anti-CD3. In addition, the CD8+ T cell subsets CD28+ and CD28- from the HIV+ and the aged groups were evaluated for cytokine production by flow cytometry, and compared with those from young controls.

Enhanced interferon-gamma by CD8+ CD28- lymphocytes from HIV+ patients.

Flow cytometric analysis of T cells from HIV+ and normal individuals activated for 15 hr showed that the percentage of cells producing interferon-gamma (INFgamma) was enhanced approximately threefold (39 compared to 14%) in the HIV+ CD8+ population. Activation modes, other than anti-CD3 with PMA, were ineffective, and in no case did the percentage of HIV+ CD4+ T cells show increased INFgamma production over controls. Enhanced INFgamma production was not induced by either anti-CD3 or PMA alone, or anti-CD3 or ConA with anti-CD28, or enhanced by N-acetylcysteine.

The proliferative response of HIV+ T-cells (CD4+ and CD8+) are severely suppressed via CD28 coactivation.

Several studies have suggested that regulation of expression of the costimulatory molecule CD28 on the T-cell surface may play an important role in AIDS pathogenesis. In a study of T-cells from HIV+ donors, we find that activation with anti-CD3 plus anti-CD28 results in a mitogenic response which was approximately 86% suppressed for both CD4+ and CD8+ T-cells when compared to normal control cells. With PMA costimulation (instead of anti-CD28), the anti-CD3 response was suppressed much less, by 64 and 61%, respectively.

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.