分子和细胞免疫进展02.ppt

3. CD8+ T cell suppression and self tolerance Murine EAE Adjuvant-induced arthritis Mouse models of type 1 diabetes Qa-1–specific transplantation tolerance could prevent generation of alloreactive CTL (III) non–Qa-1–restricted CD8+CD28– cells Can suppress immune responses by directly interacting with antigen-presenting DCs and rendering these cells tolerogenic The suppression involves the upregulation of inhibitory Ig-like transcript 3 (ILT3) and ILT4 receptors expressed on the DCs. Specific unresponsiveness in CD4+ T helper cells. The precise function of these cells in vivo is not clear, and it is not known whether they interact with the Qa-1–restricted CD8+ suppressor cells or, alternatively, whether Qa-1–restricted T cells induce tolerogenic DCs. Reference Chen, W. et al. 2003.Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J. Exp. Med Ait-Oufella H et al. Natural regulatory T cells control the development of atherosclerosis in mice. Nat Med. 2006 Feb;12(2):178-80. Epub 2006 Feb 5 * 2.Constitute 5–10% of CD4+ T cells in normal naive mice CD25+CD4+ Tregs themselves are anergic in vitro they do not proliferate or not produce IL-2 in response to conventional T cell stimuli such as plate-or bead–bound anti-CD3, ConA, or splenic APCs. Inhibit other immune cells the most remarkable feature of CD25+CD4+ Tregs is their ability to dampen immune responses suppressing a wide variety of immune cells : the innate and the adaptive immune systems 3. Functional features 4. CD25+CD4+ Treg suppression mechanism Cell-cell contact suppression: CTLA4-B71(CD80) Wing K, Onishi Y, Prieto-Martin P, Yamaguchi T, Miyara M, Fehervari Z, Nomura T, Sakaguchi S. CTLA-4 control over Foxp3+ regulatory T cell function. Science. 2008 Oct 10;322(5899):271-5 Release cytokines : IL-10, TGF-? IV) Induced CD4+CD25+ Tregs 1. Types of Induced CD4+CD25+ Treg 1) Tr1