Activation of antigen-presenting cells by microbial products breaks self tolerance and induces autoimmune disease
Activation of antigen-presenting cells by microbial products breaks self tolerance and induces autoimmune disease
Speaker: 羅志文 Date: 2004/12/8 13:10~14:00
Commentator: 王志堯 老師 Place: 601教室
Abstract
Tolerance to self-antigen is an important mechanism which prevents us from autoimmune diseases and keeps enough repertoires of immune cells to recognize many foreign substances. It is clear that immune cells capable of recognizing self-antigens exist in normal individuals without seemingly causing harm and there are several strategies which have been understood to achieve this.1 In this paper, the authors generated the transgenic mice, which express T cell receptor (TCR) specific for the encephalitogenic myelin proteolipid (PLP) peptide 139-151, from two different H-2Smouse strains, B10.S and SJL.2 Whereas TCR transgenic SJL mice readily develop experimental autoimmune encephalomyelitis (EAE) spontaneously, TCR transgenic B10.S mice rarely develop spontaneous EAE. By comparing the difference between the two strains, they found that the relative resistance to spontaneous EAE in TCR transgenic B10.S mice is due to the low activation state and a lower T cell-activation capacity of antigen-presenting cells (APCs), not deletion or anergy of T cells. Finally, they activated APCs by some microbial products, CpG oligodeoxynucleotides and pertussis toxin, to break self-tolerance in TCR transgenic B10.S mice and induce autoimmunity. These results suggest that APCs may play a role in development of autoimmune diseases and support relationship between innate immunity and autoimmunity.3
References:
1. Walker, L.S.K. and Abbas, A.K. The enemy within: Keeping self-reactive cells at bay in the periphery. Nat. Rev. Immunol. 2, 11-19 (2002)
2. Waldner, H. et al. Fulminant spontaneous autoimmunity of the central nervous system in mice transgenic for the myelin proteolipid protein- specific T cell receptor. Proc. Natl. Acad. Sci USA97, 3412-3417 (2000)
3. Waldner, H., Colins, M. and Kuchroo, V.K. Activation of antigen-presenting cells by microbial products breaks self tolerance and induces autoimmune disease. J. Clin. Invest. 113, 990-997 (2004)