Dysregulation of B7.2 (CD86) expression on monocytes of HIV-infected individuals is associated with altered production of IL-2

T helper (Th) responses are mediated in part by immunoregulatory cytokines and the signals delivered by the costimulatory CD28-B7 pathway. In this stu dy, we have investigated the relationship between the regulation of B7 isof orm expression on antigen-presenting cells from HIV+ individuals and the pr oduction of Th cytokines. The level of expression of both B7.1 and B7.2 iso forms as measured by mean channel fluorescence was significantly decreased on freshly isolated monocytes from HIV+ individuals compared with HIV- cont rols. However, the levels of expression of B7.1 and B7.2 on both B cells an d monocytes increased significantly following culture in HIV+ individuals c ompared with HIV- controls. B7 expression is subject to regulation by immun oregulatory cytokines. Therefore, we analysed the regulation of B7 expressi on by cytokines, namely IL-10 and tumour necrosis factor-alpha (TNF-alpha), the production of which is enhanced in HIV infection and have similar inhi bitory effects on B7 expression. Two groups of HIV+ individuals were distin guished on the basis of the inhibitory effect of IL-10 and TNF-alpha on mon ocyte B7.2 expression. IL-10 inhibited B7.2 expression on monocytes from so me HIV+ individuals (termed responders) like the HIV- controls. However, in a subset of HIV+ individuals (non-responders) this inhibitory effect was l ost. Loss of inhibition of B7.2 expression by IL-10 was associated with sig nificantly reduced IL-2 production by phytohaemagglutinin (PHA) stimulated peripheral blood mononuclear cells (PBMC). These observations showing an as sociation of B7 dysregulation on monocytes and B cells with altered product ion of IL-2 may have implications in HIV immunopathogenesis.