Cytokine regulation of HIV replication induced by dendritic cell-CD4-positive T cell interactions.
It has been established that human immunodeficiency virus (HIV) replication occurs throughout the course of disease in the lymphoid tissue. We have developed a model system to study the effect of cytokines and other agents on HIV replication using cocultures of DCs and T cells that reflect the cell-to-cell interactions that occur in the microenvironment of lymphoid tissue. Dendritic cells from peripheral blood, when pulsed with small amounts of HIV, induce infection in autologous, unstimulated CD4-positive T cells. Using this system, cytokines, anti-cytokine antibodies, and inhibitors of cellular activation were added to cultures and the effects on cellular proliferation and activation and HIV production were measured. Cytokines that increased T cell proliferation, such as IL-2 and IL-4, enhanced HIV replication, while the effect of IL-12 was more complex. HIV production was inhibited by blocking endogenously produced IL-2, as well as by adding IL-10, which blocks IL-2 secretion, antigen-presenting cell function, and T cell activation. Proinflammatory cytokines induced modest enhancement of viral replication in cocultures of HIV-pulsed DCs and CD4-positive T cells. Thus, using a model of HIV replication that more closely mimics the in vivo microenvironment of lymphoid tissue may allow a better analysis of the effect of cytokines and cytokine networks, as well as agents that modify immune activation on HIV replication.
Weissman
D
D
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Daucher
J
J
Barker
T
T
Adelsberger
J
J
Baseler
M
M
Fauci
A S
AS
D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002450:Cell Communication; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000494:pharmacology*; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
D016207:Cytokines; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor