Subset- and Antigen-Specific Effects of Treg on CD8+ T Cell Responses in Chronic HIV Infection

PLoS Pathogens

Maria Nikolova¹  Maria Muhtarova¹  Yves Lévy²  Aurélie Wiedemann²  Daniela Achkova³  Christine Lacabaratz⁴ 

[1] INSERM, U955, Créteil, France;Immunology Department, National Center of Infectious and Parasitic Diseases, Sofia, Bulgaria;Université Paris Est Créteil, Faculté de Médecine, Créteil, France;Vaccine Research Institute, Créteil, France

关键词: Regulatory T cells;    Cytotoxic T cells;    T cells;    HIV infections;    HIV;    Cell differentiation;    Apoptosis;    Immune response;   

DOI  :  10.1371/journal.ppat.1005995

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

We, and others, have reported that in the HIV-negative settings, regulatory CD4+CD25highFoxP3+ T cells (Treg) exert differential effects on CD8 subsets, and maintain the memory / effector CD8+ T cells balance, at least in part through the PD-1/PD-L1 pathway. Here we investigated Treg–mediated effects on CD8 responses in chronic HIV infection. As compared to Treg from HIV negative controls (Treg/HIV-), we show that Treg from HIV infected patients (Treg/HIV+) did not significantly inhibit polyclonal autologous CD8+ T cell function indicating either a defect in the suppressive capacity of Treg/HIV+ or a lack of sensitivity of effector T cells in HIV infection. Results showed that Treg/HIV+ inhibited significantly the IFN-γ expression of autologous CD8+ T cells stimulated with recall CMV/EBV/Flu (CEF) antigens, but did not inhibit HIV-Gag–specific CD8+ T cells. In cross-over cultures, we show that Treg/HIV- inhibited significantly the differentiation of either CEF- or Gag-specific CD8+ T cells from HIV infected patients. The expression of PD-1 and PD-L1 was higher on Gag-specific CD8+ T cells as compared to CEF-specific CD8+ T cells, and the expression of these markers did not change significantly after Treg depletion or co-culture with Treg/HIV-, unlike on CEF-specific CD8+ T cells. In summary, we show a defect of Treg/HIV+ in modulating both the differentiation and the expression of PD-1/PD-L1 molecules on HIV-specific CD8 T cells. Our results strongly suggest that this particular defect of Treg might contribute to the exhaustion of HIV-specific T cell responses.

【 授权许可】

CC BY