THE ROLE OF CO-STIMULATION IN REGULATION OF CHEMOKINE RECEPTOR EXPRESSION AND HIV-1 INFECTION IN PRIMARY T-LYMPHOCYTES

Fusion and entry of the human immunodeficiency virus (HN) into CD4(+) T lymphocytes requires expression of CD4 and a coreceptor. At least ei ght chemokine receptors can serve as coreceptors for HIV. Accumulating evidence indicates that multiple factors, including the state of cell ular differentiation and activation, regulate the expression of alpha- and beta-chemokine receptors on lymphocytes. For example, binding of antibodies to the CD28 coreceptor can downregulate expression of beta- chemokine receptors, and this appears to have important consequences o n the susceptibility of CD4(+) T lymphocytes to infection by HIV. In c ontrast, binding of the natural CD28 ligand B7 or antibodies to the CD 28 homologue CTLA-4 can upregulate CCR5 expression, suggesting a recip rocal interaction between CD28 and CTLA-4 and the regulation of beta-c hemokine receptor expression. Thus, the CD28/ CTLA-4/B7 co-stimulation pathway is identified as a potential novel target for the control of susceptibility to some strains of HIV-1 infection.