Cytokine Regulation of HIV Replication Induced by Dendritic Cell–CD4-Positive T Cell Interactions

Abstract

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.

Suppression of HIV replication by lymphoid tissue CD8+cells correlates with the clinical state of HIV-infected individuals

“…The in vitro studies of the present report suggest one possible mechanism (CD8 ϩ cell response) by which HIV can be controlled at the lymphoid site where cells exist in an activated state and are particularly susceptible to HIV infection (25,26). The number of subjects of the present report is limited due to the difficulty in obtaining lymphoid tissues.…”

Macaques with Rapid Disease Progression and Simian Immunodeficiency Virus Encephalitis Have a Unique Cytokine Profile in Peripheral Lymphoid Tissues

“…The association of altered cytokine expression with higher viral burden in lymph nodes may reflect the inductive effects of IL-2 and IL-6 on virus replication, as has been reported with HIV replication in vitro (1,4,20,29). Alternatively, IL-2 may increase CCR5 expression in CD4 ϩ T cells as has been recently reported with HIV infection in vivo (35), potentially increasing the number of mononuclear cells susceptible to infection with HIV and SIV.…”

Cytokines and Cell Surface Molecules Independently Induce CXCR4 Expression on CD4+ CCR7+ Human Memory T Cells

“…The importance of the interaction of dendritic cells and T cells in the transmission of HIV has been reported extensively in the literature (19,21,22,(41)(42)(43). In addition, the ability of dendritic cells to augment infection of T cells by HIV T tropic strains was found to be mediated, at least in part, by the interaction of CD40 and its ligand (44).…”