The production of HIV suppressive factors by CD28, CD38 and HLA-DR subpopulations of CD8+ T cells.

Abstract

We have examined CD8+ sub-populations to determine whether these subsets are critical to the production of CD8+ T cell nonlytic factors. The production of the beta-chemokines MIP-1alpha, MIP-1beta and RANTES, and the chemoattractant cytokine IL-16 were measured in cells derived from 24 HIV-infected and 25 uninfected subjects. Asymptomatic HIV+ subjects (CD4 > 200/ul) produced significantly higher levels of MIP-1alpha and MIP-1beta from CD8+ T cells and some sub-phenotypes. Higher RANTES levels were produced by CD28-, CD38- and HLA-DR+/- sub-phenotypes. However, IL-16 was only modulated in the CD38+ subset in comparison to total CD8+ T cells. Infection of CD8+ T cells and sub-populations resulted in generally increased levels of chemokine and IL-16 production, which dissipated over a 15 day time course. Moreover, CD8+ antiviral factor (CAF) activity, another major component of CD8+ T cell nonlytic suppression factors, was not associated with chemokine production. However, significantly higher levels of CAF were produced by CD38+ and HLA-DR+ sub-populations. In addition, we also showed that in CD8+ T cell populations, the production of MIP-1alpha, MIP-1beta and IL-16 was inversely correlated with virus copy number. These findings shed light on the noncytotoxic responses of CD8+ T cells in controlling the natural course of HIV infection.