Clarification of the role of CD8^+CD122^+ regulatory T cells in vivo and development of their clinical applications

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1. Mechanism of the effect of CD8^+CD122^+ regulatory T cellsWe investigated how murine CD8^+CD122^+ regulatory T cells suppress their target cells by using in vitro culture systems. As a result, we found that these regulatory T cells directly recognized activated T cells without intervention of antigen-presenting cells and regulated them. The interactions between MHC class I and T cell receptor and between CD28 and CD80/CD86 were important in the process of regulation. The regulatory T cells that had recognized their target cells became active regulatory cells and regulated them by producing IL-10.2. Effect of CD8^+CD122^+ regulatory T cells on autoimmune diseasesWe investigated on the effect of CD8^+CD122^+ regulatory T cells using murine model of EAE (Experimental Autoimmune Encephalomyelitis). In mice that had been treated with anti-CD122 antibody that depleted CD8^+CD122^+ regulatory T cells, symptoms of EAE continued for more than6 weeks without improvement. On the other hand, tr … More ansfer of CD8^+CD122^+ regulatory T cells into those mice that had been treated with anti-CD122 antibody and continued the EAE symptoms at thepeak level dramatically caused the quick reduction of EAE symptoms. Thus, it was clearly proved that CD8^+CD122^+ regulatory T cells play an important role in the recovery from the disease that based on the anomaly of immune system.3. Search for human regulatory T cellsBecause there are no CD8^+CD122^+ cells in human, we needed to search human CD8^+ regulatory T cells using other markers than CD122. We performed DNA micro-array analysis to compare the gene expression profile between CD8^+CD122^+ cells and CD8^+CD122^- cells. We found CXCR3 as a candidate gene, and actually the expression of CD122and that of CXCR3was well correlated in mouse CD8^+cells. There are also human CD8^+ cells that express CXCR3and such CD8^+CXCR3^+ cells showed immune regulating activity such as suppressing the production of IFN_γ from the CD8^+CXCR3 cells. Thus, CD8^+CXCR3^+ cells work as regulatory T cells that correspond to murine CD8^+CD122^+ cells. Less