TGF-beta and IL-10 production by HIV-specific CD8+ T cells is regulated by CTLA-4 signaling on CD4+ T cells.
Immune dysregulation in HIV-1 infection is associated with increased expression of inhibitory molecules such as CTLA-4, TGF-beta, and IL-10. In this study we examined one potential mechanism for regulating TGF-beta and IL-10 expression by HIV-specific suppressor CD8+ T cells. No overlap between TGF-beta, IL-10, and IFN-gamma cytokine production by HIV-specific CD8+ T cells was observed. TGF-beta positive and IL-10 positive cells were FOXP3 negative, CD25 negative, and displayed a heterogeneous surface expression of CD127. TGF-beta 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-beta positive and IL-10 positive CD8+ T cell responses, and a concomitant increase in HIV-specific IFN-gamma positive CD8+ T cell responses. Depletion of CD4+ T cells abrogated the impact of CTLA-4 on HIV-specific TGF-beta 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.
Elrefaei
Mohamed
M
California Department of Public Health, Richmond, California, USA.
Burke
Candace M
CM
Baker
Chris A R
CA
Jones
Norman G
NG
Bousheri
Stephanie
S
Bangsberg
David R
DR
Cao
Huyen
H
D015703:Antigens, CD / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D060908:CTLA-4 Antigen; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis*; D018125:Receptors, Transforming Growth Factor beta; D015398:Signal Transduction / Q000276:immunology; D013045:Species Specificity; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D007371:Interferon-gamma