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 Bangsberg, Huyen Cao

Research output: Contribution to journalArticle

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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
Externally publishedYes

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T-cells
interleukin-10
Interleukin-10
T-lymphocytes
HIV
T-Lymphocytes
Human immunodeficiency virus 1
HIV Infections
HIV-1
cytokines
Cells
Cytokines
Molecules

ASJC Scopus subject areas

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

Cite this

TGF-β and IL-10 production by HIV-specific CD8+ T cells is regulated by CTLA-4 signaling on CD4+ T cells. / Elrefaei, Mohamed; Burke, Candace M.; Baker, Chris A R; Jones, Norman G.; Bousheri, Stephanie; Bangsberg, David; Cao, Huyen.

In: PLoS One, Vol. 4, No. 12, e8194, 2009.

Research output: Contribution to journalArticle

Elrefaei, Mohamed ; Burke, Candace M. ; Baker, Chris A R ; Jones, Norman G. ; Bousheri, Stephanie ; Bangsberg, David ; Cao, Huyen. / TGF-β and IL-10 production by HIV-specific CD8+ T cells is regulated by CTLA-4 signaling on CD4+ T cells. In: PLoS One. 2009 ; Vol. 4, No. 12.
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