HIV-specific TGF-beta-positive CD4+ T cells do not express regulatory surface markers and are regulated by CTLA-4.
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.
Elrefaei
Mohamed
M
California Department of Public Health , Richmond, California 94804, USA. melrefae@unch.unc.edu
Burke
Candace M
CM
Baker
Chris A R
CA
Jones
Norman G
NG
Bousheri
Stephanie
S
Bangsberg
David R
DR
Cao
Huyen
H
D056704:Adaptive Immunity; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D000954:Antigens, Surface / Q000096:biosynthesis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D060908:CTLA-4 Antigen; D051858:Forkhead Transcription Factors / Q000096:biosynthesis* / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D015497:HIV-1; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis* / Q000276:immunology; D053699:Interleukin-7 Receptor alpha Subunit / Q000096:biosynthesis* / Q000276:immunology; D017346:Protein Serine-Threonine Kinases / Q000276:immunology / Q000378:metabolism; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000276:immunology
D015703:Antigens, CD; D000954:Antigens, Surface; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II