Role of CD25+ and CD25-T cells in acute HIV infection in vitro.

Abstract

T cell activation plays a major role in the ability of the HIV to remain latent or establish a productive infection. The alpha-chain of the IL-2R (CD25, Tac, p55) is expressed on activated but not resting T cells and therefore represents an ideal marker to distinguish activated from resting T cells. The present studies were designed to define the role of CD25+ (activated) and CD25- (resting) T cells in an acute HIV infection in vitro. This objective was accomplished by selectively killing CD25+ cells with an anti-CD25-ricin A chain immunotoxin (RFT5-deglycosylated ricin A (dgA)) either before or after HIV infection, and then determining the effect of eliminating these cells on the secretion of viral p24 Ag. Three major findings have emerged from this study: 1) Elimination of the small population (3 to 5%) of activated, CD25+ cells present in normal PBMC before HIV infection results in a 99% reduction in p24 secretion. 2) RFT5-dgA, an immunotoxin directed against CD25, kills HIV-infected CD25+ cells. Elimination of the CD25+ cells after infection with HIV virtually stops viral production and the spread of the infection in these cultures. This was confirmed by coculturing RFT5-dgA-treated PBMC with H9 cells. 3) When RFT5-dgA-treated PBMC (CD25-cells) were infected with HIV and then activated with a solid phase anti-CD3 mAb, the levels of p24 produced were comparable with those of PBMC from which the CD25+ cells had not been eliminated. Taken together these findings suggest that both activated (CD25+) and resting/quiescent (CD25-) cells can be infected with HIV but that only the CD25+ cells produce viral proteins in the absence of additional activation.