The APCs of autoimmune disease

Automimmune diseases are a complex set of disorders that all result from a failure of the immune system to recognize "self" due to the presence of autoreactive T cells. The body has several means of removing autoreactive T cells, including T cell deletion in the thymus and peripheral tolerance for T cells that escape thymic deletion. These mechanisms, however, fail in some individuals, resulting in an autoimmune response that can be crippling. Many of the factors, both environmental and genetic, involved in autoimmune disease development remain a mystery. Vijay Kuchroo and colleagues of Brigham and Woman's Hospital and Harvard Medical School used autoreactive transgenic T cells in an experimental autoimmune encephalomyelitis (EAE)–resistant mouse strain and now present data showing that the activation state of APCs plays a role in the development of autoimmune diseases (pages 990–997). T cell number and response were the same in both the transgenic EAE-resistant and EAE-sensitive backgrounds; however, the APCs in the EAE-resistant background had a lower activation state and lower T cell stimulating response than those in the EAE-sensitive strain. Furthermore, innate immune receptor activation of the APCs resulted in EAE development even in the resistant background, providing insight into why viral infection is often associated with the onset of certain autoimmune disorders.

TITLE: Activation of antigen-presenting cells by microbial products breaks self tolerance and induces autoimmune disease

AUTHOR CONTACT:
Vijay K. Kuchroo
Brigham and Women's Hospital and Harvard Medical School, Cambridge, Massachusetts, USA.
Phone: 617-525-5350
Fax: 617-525-5333
E-mail: vkuchroo@rics.bwh.harvard.edu

View the PDF of this article at: http://www.jci.org/cgi/content/full/113/7/990

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