TGF-β and IL-10 production by HIV-specific CD8+ T cells is regulated by CTLA-4 signaling on CD4+ T cells

Mohamed Elrefaei, Candace M. Burke, Chris A.R. Baker, Norman G. Jones, Stephanie Bousheri, David R. Bangsberg, Huyen Cao

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Immune dysregulation in HIV-1 infection is associated with increased expression of inhibitory molecules such as CTLA-4, TGF-b, and IL-10. In this study we examined one potential mechanism for regulating TGF-b and IL-10 expression by HIV-specific suppressor CD8+ T cells. No overlap between TGF-b, IL-10, and IFN-c cytokine production by HIV-specific CD8+ T cells was observed. TGF-b positive and IL-10 positive cells were FOXP3 negative, CD25 negative, and displayed a heterogeneous surface expression of CD127. TGF-b and IL-10 positive CD8+ T cells did not express CTLA-4. Nevertheless, CTLA-4 blockade resulted in a significant decrease in HIV-specific TGF-b positive and IL-10 positive CD8+ T cell responses, and a concomitant increase in HIV-specific IFN-c positive CD8+ T cell responses. Depletion of CD4+ T cells abrogated the impact of CTLA-4 on HIV-specific TGF-b positive and IL-10 positive CD8+ T cells. Our study suggests that CTLA-4 Signaling on CD4+ T cells regulates the inhibitory functions of the HIV-specific suppressor CD8+ T cells.

Original languageEnglish (US)
Article numbere8194
JournalPloS one
Volume4
Issue number12
DOIs
StatePublished - 2009

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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