CYTOKINE REGULATION OF HIV REPLICATION INDUCED BY DENDRITIC CELL CD4-POSITIVE T-CELL INTERACTIONS

It has been established that human immunodeficiency virus (HIV) replic ation 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 th at reflect the cell-to-cell interactions that occur in the microenviro nment of lymphoid tissue. Dendritic cells from peripheral blood, when pulsed with small amounts of HIV, induce infection in autologous, unst imulated CD4-positive T cells. Using this system, cytokines, anti-cyto kine antibodies, and inhibitors of cellular activation were added to c ultures and the effects on cellular proliferation and activation and H IV production were measured. Cytokines that increased T cell prolifera tion, such as IL-2 and IL-4, enhanced HIV replication, while the effec t 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 I L-2 secretion, antigen-presenting cell function, and T cell activation . Proinflammatory cytokines induced modest enhancement of viral replic ation 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 mod ify immune activation on HIV replication.