HIV replication in IL-2-stimulated peripheral blood mononuclear cells is driven in an autocrine/paracrine manner by endogenous cytokines

A. L. Kinter, G. Poli, L. Fox, E. Hardy, A. S. Fauci

Research output: Contribution to journalArticlepeer-review

Abstract

Replication of HIV is regulated by virus-encoded regulatory proteins, as well as by a variety of cellular factors including cytokines. In the present study, we have investigated the autocrine/paracrine effects of endogenous cytokines on HIV replication in primary PBMCs of healthy HIV seronegative individuals. Addition of rIL-2 to cultures between 0 and 72 h after isolation of PBMCs allowed the replication of primary HIV isolates and laboratory- adapted HIV strains to levels comparable with or greater than those obtained in parallel cultures of autologous PHA-blasts. In this regard, both major cellular targets of HIV infection, CD4+ T lymphocytes and mononuclear phagocytes, were maintained for several weeks in IL-2-stimulated PBMC cultures and virion production was observed in both cell lineages. The kinetics of secretion of several cytokines (such as TNF-α, IL-1β, IL-6, and IFN-γ), as well as expression of cellular activation markers, paralleled HIV replication in IL-2-stimulated PBMCs. Endogenous pro-inflammatory cytokines and IFN-γ, played a major role in the regulation of HIV replication in IL- 2-stimulated PBMCs, as determined by the ability of several anti-cytokine Abs or antagonists to suppress HIV production; this was not the case in parallel cultures of autologous PHA-blasts. Thus, IL-2-stimulated PBMCs may represent a more physiologic in vitro system than PHA-blasts for the study of HIV infection and replication, and should prove useful in investigating the role of cytokines and other host factors in the regulation of HIV production.

Original languageEnglish
Pages (from-to)2448-2459
Number of pages12
JournalJournal of Immunology
Volume154
Issue number5
Publication statusPublished - 1995

ASJC Scopus subject areas

  • Immunology

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