Reversal of the inhibitory effects of HIV-gp120 on CD4+ T cells by stimulation through the CD28 pathway

A. Faith, H. Yssel, R. E. O'Hehir, J. R. Lamb

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Abstract

The effects of exposure to HIV-gp 120 on proliferation and cytokine production by T cell lines were investigated. T cell lines were generated by stimulation of peripheral blood mononuclear cells from several healthy donors with cross-linked anti-CD3 antibodies and IL-2. These T cell lines exhibited the characteristics of Th1 cells, producing IL-2 and interferon-gamma (IFN-γ), but not IL-4, on stimulation with anti-CD3 antibodies. In the presence of gp120, stimulation with anti-CD3 antibodies was inhibited in terms of both proliferative responses and the secretion of IL-2 and IFN-γ. Similar effects were observed when a T cell line was stimulated in the presence of a synthetic peptide representing the CD4-binding region of gp120. Neither gp120 nor the CD4-binding region peptide had any effect on IL-4 production by the T cell lines. Stimulation through the CD28 pathway partially restored both the proliferative effect and cytokine production by T cell lines in response to anti-CD3 antibodies in the presence of gp120. Anti-CD28 antibodies also partially restored cytokine production when purified CD4+ T cells from a T cell line were stimulated with anti-CD3 antibodies in the presence of gp120. Anti-gp120 antibodies partially or completely reversed the inhibitory effects of gp120 on T cell proliferation. These results indicate that stimulation through the CD28 pathway may restore defective CD4+ T cell responses in HIV-infected individuals.

Original languageEnglish
Pages (from-to)225-230
Number of pages6
JournalClinical and Experimental Immunology
Volume105
Issue number2
DOIs
Publication statusPublished - 1 Jan 1996
Externally publishedYes

Keywords

  • Cytokines
  • gp120
  • Inhibition
  • T cells
  • Th1

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