Role of CD25+ and CD25-T cells in acute HIV infection in vitro.
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.
Department of Microbiology, University of Texas Southwestern Medical, Center, Dallas 75235-9048.
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Ramilo
K D
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Bell
J W
JW
Uhr
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ES
Vitetta
D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006678:HIV / Q000187:drug effects / Q000254:growth & development* / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D012276:Ricin / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000382:microbiology / Q000502:physiology*
D000922:Immunotoxins; D015375:Receptors, Interleukin-2; D012276:Ricin