Thursday, April 4th – 16.15Professor Shimon Sakaguchi
Department of Experimental Immunology, WPI Immunology Frontier Research Center, Osaka University, Osaka, JapanTitle: “Regulatory T cells for immune tolerance and homeostasis”
The normal immune system protects the individual from pathogenic microbes while avoiding harmful reactions against the constituents of the body. To understand how this immunological self-tolerance is maintained or, more generally, how aberrant or excessive immune reactions are controlled has been a key issue in immunology and medicine. There is accumulating evidence that a T cell subpopulation, called regulatory T cells (Tregs), is present in the immune system and is actively engaged in the maintenance of immune self-tolerance and homeostasis. They were first characterized as CD4+ T cells constitutively expressing CD25 (interleukin-2 receptor) and later as specifically expressing the transcription factor Foxp3. A cardinal feature of Foxp3+CD25+CD4+ natural Tregs, which physiologically constitute ~10% of CD4+ T cells, is that the majority of them are produced by the normal thymus as a functionally mature and distinct population specialized for immune suppression. Deficiency of natural Tregs or mutations of Foxp3 indeed produces a variety of autoimmune diseases, allergy, and immunopathological diseases such as inflammatory bowel disease in rodents and humans. In addition, reduction of Tregs evokes effective tumor immunity while antigen-specific expansion of Tregs induces transplantation tolerance. In this lecture, I shall discuss the molecular and cellular basis of Treg development and function and how they can be exploited in clinical settings.
1. Sakaguchi, S., Yamaguchi, T., Nomura, T., and Ono, M. Regulatory T cells and immune tolerance. Cell 133, 775-787 (2008).
2. Wing, K., and Sakaguchi, S. Regulatory T cells exert checks and balances on self-tolerance and autoimmunity. Nat. Immunol. 11, 7-13 (2010).