Enhanced interferon-γ 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 (INF gamma) 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 INF gamma production over controls. Enhanced INF gamma production was not induced by either anti-CDS or PMA alone, or anti-CD3 or ConA with anti-CD28, or enhanced by N-acetylcysteine. In contrast to INF gamma production, the percentage of CD4(+) T cells producing interleukin-2 (IL-2) greatly exceeded that of the CD8(+) T cells. The results from flow cytometry analyses of HIV+ CD8(+) T cells was supported by quantitative analysis of INF gamma mRNA (by PCR) and INF gamma secretion by ELISA. These methods showed a sixfold and three- to fivefold increase, respectively, on a per cell basis. As HIV infection progresses, as shown by loss of CD4(+) T cells, the proportion of CD8(+) CD28(-) T cells increases, and it is this T cell subset that is responsible for 80% or more of the enhanced INF gamma production. The enhanced INF gamma in HIV+ patients derives from two factors: the increase in CD8(+) CD28(-) cells to 70% and the percentage producing INF gamma (60%, compared to 21% for CD8(+) CD28(+) cells). Our findings of a substantial increase in INF gamma production in HIV infection arising from the increased number of CD8(+) CD28(-) T cells are compatible with clinical studies which show elevated INF gamma in HIV+ serum and INF gamma producing CD8(+) T cells dominating HIV+ lymph nodes. We also found a significantly decreased proliferative response of the HIV+-derived CD8(+) T cell fraction with coactivator anti-CD-28, in contrast to PMA (with anti-CD3), which is probably a reflection of the diminished population of CD8(+) CD28(+) T cells in HIV+ donors compared to normal donors (30.7 compared to 67.9%).