Differential regulation of HIV-1 fusion cofactor expression by CD28 costimulation of CD4+ T cells.

Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.

Differential regulation of HIV-1 fusion cofactor expression by CD28 costimulation of CD4+ T cells.

Conf Adv AIDS Vaccine Dev. 1997 May 4-7;:20. Unique Identifier : AIDSLINE MED/97927012
June CH; Riley JL; Levine BL; Feng Y; Kaushal S; Ritchey DW; Bernstein W; Weislow OS; Berger EA; St. Louis DC; Carroll RG; Division of Retrovirology, Walter Reed Army Institute for Research,; Bethesda, MD. Fax: (301) 295-6484.

Abstract: A potent anti-viral effect was found to be mediated by certain forms of CD28 signal transduction. CD28 receptor costimulation can lead to polyclonal expansion of CD4+ cells from HIV-infected donors during cell culture. Moreover, CD28 stimulation rendered CD4+ cells from uninfected donors highly resistant to HIV-1 infection. Induction of HIV-1 resistance was specific for CD28 costimulation in that a variety of other accessory receptors such as CD2, CD4, CD5 and MHC class I failed to confer the anti-viral resistance. Furthermore, the effect is specific for macrophage-tropic strains of HIV-1. Analysis of strong stop DNA transcripts showed that the CD28-mediated anti-viral effect was early in the viral life cycle, prior to HIV-1 DNA integration. Transcripts encoding CXCR4/Fusin, the fusion cofactor used by T cell line-tropic isolates, were abundant in CD3/CD28-stimulated cells, but transcripts encoding CCR5, the fusion cofactor used by macrophage-tropic viruses, were not detectable. The inhibitory effect of CD28 stimulation on CCR5 expression was dominant over the L-2 mediated activation effects on CCR5. Thus, CD3/CD28 costimulation induces an HIV-1-resistant phenotype in vitro similar to that seen in some highly exposed and uninfected individuals. Interim results from a phase I clinical trial testing the adoptive transfer of CD4 cells after ex vivo activation with anti-CD3 and CD28 antibody will be presented. Together these findings suggest that manipulation of the CD28 signal transduction pathway has therapeutic potential for the treatment of HIV-1 infection.

Keywords: *Antigens, CD28/IMMUNOLOGY *CD4-Positive T-Lymphocytes/IMMUNOLOGY *HIV-1/GENETICS *Membrane Fusion
971130
M97B1204

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