Suppressive activity of regulatory T cells correlates with high CD4(+) T-cell counts and low T-cell activation during chronic simian immunodeficiency virus infection.

Abstract

OBJECTIVE: HIV/simian immunodeficiency virus (SIV) infection is characterized by progressive CD4(+) T-cell depletion and immune exhaustion. CD25(+)FoxP3(+) regulatory T cells were evidenced in HIV/SIV infection and disease. They could be positive by suppressing immune activation during chronic infection and/or damper T-cell immunity. Here we evaluated the correlation between regulatory T-cell function and disease progression in pathogenic SIV infection. DESIGN: We compared the in-vitro suppressive capacity of CD25(+) cells from peripheral blood and peripheral lymph nodes of 18 SIVmac251-infected cynomolgus macaques to look for correlates with biological markers of progression to disease. METHODS: The in-vitro suppressive capacity of CD25(+) cells was evaluated in a proliferation assay. Ex-vivo T-cell activation was determined by phenotypic labeling followed by flow cytometry. RESULTS: In chronic infection, CD25(+) regulatory T-cell activity correlated to preserved CD4 T-cell counts and lower T-cell activation. CONCLUSION: This study suggests that regulatory T-cell function is lost during disease progression and may have a positive impact on HIV/SIV disease.