title: HIV replication in IL-2-stimulated peripheral blood mononuclear cells is driven in an autocrine/paracrine manner by endogenous cytokines.
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-alpha, IL-1 beta, IL-6, and IFN-gamma), as well as expression of cellular activation markers, paralleled HIV replication in IL-2-stimulated PBMCs. Endogenous pro-inflammatory cytokines and IFN-gamma 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.
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: A L
authors.initials: AL
authors.lastname: Kinter
authors.forename: G
authors.initials: G
authors.lastname: Poli
authors.forename: L
authors.initials: L
authors.lastname: Fox
authors.forename: E
authors.initials: E
authors.lastname: Hardy
authors.forename: A S
authors.initials: AS
authors.lastname: Fauci
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D016207:Cytokines / Q000502:physiology*; D015497:HIV-1 / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000502:physiology; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000502:physiology; D007376:Interleukin-2 / Q000494:pharmacology; D015850:Interleukin-6 / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000145:classification / Q000276:immunology / Q000821:virology*; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology / Q000821:virology; D008954:Models, Biological; D009000:Monocytes / Q000276:immunology / Q000821:virology; D009500:Neutralization Tests; D012795:Sialoglycoproteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D014779:Virus Replication / Q000276:immunology / Q000502:physiology
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma