suppression of hiv-specific and allogeneic t cell activation by human regulatory t cells is dependent on the strength of signalshiv-specific和同种异体t细胞激活的抑制人类的调节性t细胞是依赖于信号的强度.pdfVIP

Suppression of HIV-Specific and Allogeneic T Cell Activation by Human Regulatory T Cells Is Dependent on the Strength of Signals 1 3 1,2 3 Amanda K. Antons , Rui Wang , Spyros A. Kalams , Derya Unutmaz * 1 Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America, 2 Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America, 3 Department of Microbiology, New York University School of Medicine, New York, New York, United States of America Abstract Regulatory T cells (Tregs) suppress immune responses against both self and non-self antigens. Tregs require activation through the T cell receptor (TCR) and IL-2 to exert their suppressive functions. However, how strength of TCR signals modulate the potency of Treg-mediated suppression of antigen-specific T cell activation remain unclear. We found that both strength of TCR signals and ratios of Tregs to target cells, either through superantigen, allogeneic antigens or HIV- specific peptides, modified the suppressive ability of Tregs. While human Tregs were able to mediate suppression in the presence of only autologous antigen-presenting cells, this was much less efficient as compared to when Tregs were activated by allogeneic dendritic cells. In another physiologically relevant system, we show that the strength of peptide stimulation, high frequency of responder CD8+ T cells or presence of high IL-2 can override the suppression of HIV-specific CD8+ T cells by Tregs. These findings suggest that ratios and TCR activation of human Tregs, are important parameters to overcome robust immune responses to pathogens or allogeneic anti