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 study, we have investigated the relationship between the regulation of B7 isoform expression on antigen-presenting cells from HIV+ individuals and the production of Th cytokines. The level of expression of both B7.1 and B7.2 isoforms as measured by mean channel fluorescence was significantly decreased on freshly isolated monocytes from HIV+ individuals compared with HIV- controls. However, the levels of expression of B7.1 and B7.2 on both B cells and monocytes increased significantly following culture in HIV+ individuals compared with HIV- controls. B7 expression is subject to regulation by immunoregulatory cytokines. Therefore, we analysed the regulation of B7 expression by cytokines, namely IL-10 and tumour necrosis factor-alpha (TNF-alpha), the production of which is enhanced in HIV infection and have similar inhibitory effects on B7 expression. Two groups of HIV+ individuals were distinguished on the basis of the inhibitory effect of IL-10 and TNF-alpha on monocyte B7.2 expression. IL-10 inhibited B7.2 expression on monocytes from some HIV+ individuals (termed responders) like the HIV- controls. However, in a subset of HIV+ individuals (non-responders) this inhibitory effect was lost. Loss of inhibition of B7.2 expression by IL-10 was associated with significantly reduced IL-2 production by phytohaemagglutinin (PHA)- stimulated peripheral blood mononuclear cells (PBMC). These observations showing an association of B7 dysregulation on monocytes and B cells with altered production of IL-2 may have implications in HIV immunopathogenesis.
Division of Virology and Molecular Immunology, Research Institute, Children's Hospital of Eastern Ontario, Canada. akumar@med.uottawa.c
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Kumar
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Angel
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Diaz-Mitoma
D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology; D051940:B7-2 Antigen; D005786:Gene Expression Regulation / Q000187:drug effects; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008211:Lymphocyte Cooperation / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015703:Antigens, CD; D051940:B7-2 Antigen; C497964:CD86 protein, human; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10