Altered phenotype of regulatory T cells associated with lack of human immunodeficiency virus (HIV)-1-specific suppressive function

作者：Burton C T; Westrop S J; Eccles James I; Boasso A; Nelson M R; Bower M; Imami N^*

来源：Clinical and Experimental Immunology, 2011, 166(2): 191-200.

DOI：10.1111/j.1365-2249.2011.04451.x

• anergy/suppression/tolerance
• HIV-1
• T cells

Mechanisms by which CD4(+) regulatory T cells (T(regs)) mediate suppression of virus-specific responses remain poorly defined. Adenosine, mediated via CD39 and CD73, has been shown to play a role in the action of murine T(regs). In this study we investigate the phenotype of T(regs) in the context of human immunodeficiency virus (HIV)-1 infection, and the function of these cells in response to HIV-1-Gag and cytomegalovirus (CMV) peptides. Phenotypic data demonstrate a decrease in forkhead box transcription factor 3 (FoxP3(+)) T(reg) numbers in the peripheral blood of HIV-1(+) individuals compared to healthy controls, which is most pronounced in those with high HIV-1 RNA plasma load. Due to aberrant expression of CD27 and CD127 during HIV-1 disease, these markers are unreliable for T(reg) identification. The CD3(+) CD4(+) CD25hiCD45RO(+) phenotype correlated well with FoxP3 expression in both the HIV-1(+) and seronegative control cohorts. We observed expression of CD39 but not CD73 on T(regs) from HIV-1(+) and healthy control cohorts. We demonstrate, through Treg depletion, the suppressive potential of T(regs) over anti-CMV responses in the context of HIV-1 infection; however, no recovery of the HIV-1-specific T cell response was observed indicating a preferential loss of HIV-1-specific Treg function. We propose that before immunotherapeutic manipulation of T(regs) is considered, the immunoregulatory profile and distribution kinetics of this population in chronic HIV-1 infection must be elucidated fully.

• 出版日期2011-11