regulatory t cells suppress natural killer cells during plasmid dna vaccination in mice, blunting the cd8+ t cell immune response by the cytokine tgfβ调节性t细胞抑制自然杀伤细胞在质粒dna疫苗在小鼠体内,削弱cd8 + t细胞免疫反应的细胞因子tgfβ.pdfVIP

Regulatory T Cells Suppress Natural Killer Cells during Plasmid DNA Vaccination in Mice, Blunting the CD8+ T Cell Immune Response by the Cytokine TGFb 1 2 1 Kwesi Frimpong-Boateng , Nico van Rooijen , Ralf Geiben-Lynn * 1 Division of Viral Pathogenesis, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America, 2 Department of Molecular Cell Biology, Vrije University Medical Center, Amsterdam, The Netherlands Abstract + + Background: CD4 CD25 regulatory T cells (Tregs) suppress adaptive T cell-mediated immune responses to self- and foreign-antigens. Tregs may also suppress early innate immune responses to vaccine antigens and might decrease vaccine efficacy. NK and NKT cells are the first responders after plasmid DNA vaccination and are found at the site of inoculation. Earlier reports demonstrated that NKT cells could improve plasmid DNA efficacy, a phenomenon not found for NK cells. In fact, it has been shown that under certain disease conditions, NK cells are suppressed by Tregs via their release of IL-10 and/ or TGFb. Therefore, we tested the hypothesis that NK cell function is suppressed by Tregs in the setting of plasmid DNA vaccination. Methodology/Principal Findings: In this study we show that Tregs directly inhibit NK cell function during plasmid DNA vaccination by suppressing the potentially 10-fold, NK cell-mediated, augmentation of plasmid DNA antigen-specific CD8+ T cells. We found that this phenomenon is dependent on the secretion of cytokine TGFb by Tregs, and independent of IL-10. Conclusions: Our data indicate a crucial function for Tregs in blocking plasmid DNA vaccine-elicited immune responses, revealing potentially novel strategies for i