Abstract
CD4(+) T cell dysfunction in HIV-1 infection is associated with increased CTLA-4 and TGF-beta expression. In this study we described a population of TGF-beta-positive CD4(+) T cells with multiple HIV specificities. These HIV-specific TGF-beta-positive CD4(+) T cells did not display the immunophenotypic patterns traditionally attributed to regulatory CD4(+) T cells. TGF-beta-positive CD4(+) T cells were FOXP3 negative, CD25 negative, and displayed a heterogeneous surface expression of CD127. We also examined one potential mechanism for regulating TGF-beta expression by HIV-specific CD4(+) T cells. Blocking of the TGF-beta receptor II led to increased HIV-specific IFN-gamma-positive CD4(+) and CD8(+) T cell responses. Interestingly, HIV-specific TGF-beta-positive CD4(+) T cells did not substantially express CTLA-4. Nevertheless, CTLA-4 blockade resulted in a significant decrease in HIV-specific TGF-beta-positive CD4(+) T cell responses, and a concomitant increase in HIV-specific IFN-gamma-positive CD4(+) T cell responses. Our study proposes a mechanism by which HIV-specific TGF-beta production may be regulated by CTLA-4 engagement.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptive Immunity
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Antigens, CD / immunology
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Antigens, CD / metabolism*
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Antigens, Surface / biosynthesis
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Antigens, Surface / immunology
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism*
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CTLA-4 Antigen
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Forkhead Transcription Factors / biosynthesis*
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Forkhead Transcription Factors / immunology
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HIV Infections / immunology*
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HIV Infections / metabolism
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HIV Infections / virology
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HIV-1*
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Humans
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Interferon-gamma / biosynthesis
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Interferon-gamma / immunology
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Interleukin-2 Receptor alpha Subunit / biosynthesis*
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Interleukin-2 Receptor alpha Subunit / immunology
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Interleukin-7 Receptor alpha Subunit / biosynthesis*
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Interleukin-7 Receptor alpha Subunit / immunology
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Protein Serine-Threonine Kinases / immunology
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Protein Serine-Threonine Kinases / metabolism
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Receptor, Transforming Growth Factor-beta Type II
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Receptors, Transforming Growth Factor beta / immunology
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Receptors, Transforming Growth Factor beta / metabolism
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Transforming Growth Factor beta / biosynthesis
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Transforming Growth Factor beta / immunology
Substances
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Antigens, CD
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Antigens, Surface
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CTLA-4 Antigen
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CTLA4 protein, human
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FOXP3 protein, human
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Forkhead Transcription Factors
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IL2RA protein, human
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Interleukin-2 Receptor alpha Subunit
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Interleukin-7 Receptor alpha Subunit
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Receptors, Transforming Growth Factor beta
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Transforming Growth Factor beta
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Interferon-gamma
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Protein Serine-Threonine Kinases
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Receptor, Transforming Growth Factor-beta Type II