AEGiS-11IAC: Association of dysregulated production of IL-10 with alterations in the CD28-B7 co-stimulatory pathway in HIV infection.

11th International AIDS Conference


Vancouver, British Columbia — July 7-12, 1996

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Association of dysregulated production of IL-10 with alterations in the CD28-B7 co-stimulatory pathway in HIV infection.

Int Conf AIDS 1996 Jul 7-12; 11:225 (abstract no. Tu.A.383)
Kumar A, Creery WD, Cameron W, Diaz-Mitoma F, Filion LG; Division of Virology, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada. Fax: 613-738-4819. E-mail: akumar@Labsun1.med.uottawa.ca.

OBJECTIVE: To study the alterations in the signals delivered by the co-stimulatory molecule CD28 in CD4+ T cells and B7 receptors in monocytes/macrophages, and its association with constitutively expressed immunoregulatory cytokines IL-10 in HIV infection.

METHODS: The expression of CD28 on CD4+ and CD8+T cells and B7-1 and B7-2 isoforms on monocytes from 32 HIV-infected and 5 normal individuals was analyzed by flow cytometry. CD4+ cells were stimulated with anti CD28 antibodies and suboptimal concentrations of PHA (1:200). T cell proliferation was correlated with plasma virus load (p24) and the levels of IL-10 produced by PHA stimulated PBMC by using appropriate ELISA. Alterations in B7.2 expression on CD14+ monocytes following addition of monokines were investigated by flow cytometry.

RESULTS: CD4+ T cells, unlike CD8+ T cells, express normal levels of CD28 receptors but fail to proliferate following stimulation with anti-CD28 antibodies compared to controls indicating signalling defects at the level of the CD28 receptors. Furthermore, CD28 induced proliferation was inversely correlated with both plasma p24 levels and with the levels of IL-10 produced by PHA stimulated PBMC. Since IL-10 is overexpressed in HIV+ individuals, and IL-10 mediates its effects via B7 molecules, we studied the effects of IL-10 on the expression of B7 isoforms on CD14+ monocytes. The inhibitory effects of IL-10 and TNFalpha on the expression of B7.2 was lost in HIV+ individuals with less than 300 CD4+ T cells/microliter unlike HIV+ individuals with greater than 300 CD4+ T cells/ml and HIV-normal individuals, indicating an inactivation of these receptors.

CONCLUSIONS: Enhanced IL-10 production may be associated with alterations in signals delivered by CD28 and B7 molecules, and may have implications in immunological unresponsiveness in HIV infections.

Keywords: AEGIS, Antigens, CD28, Antigens, CD80, Interleukin-10, HIV Infections, Antigens, CD, HIV, T-Lymphocytes, Antigens, CD8, Antigens, CD4, Phytohemagglutinins, Monocytes, Anti-HIV Agents, Cytokines, HIV Core Protein p24, CD9 antigen, ICA11KWDaegis,antigens,cd28,antigens,cd80,interleukin-10,hivinfections,antigens,cd,hiv,t-lymphocytes,antigens,cd8,antigens,cd4,phytohemagglutinins,monocytes,anti-hivagents,cytokines,hivcoreproteinp24,cd9antigen,ica11

960707
TuA383

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