Editorial [Hot Topic:Controlling Autoimmunity by Modulating the Function of Autoantigen-Specific T Cells (Guest Editor: Andrew D. Weinberg)]

It has been hypothesized that T cell recognition of a self-antigen in the periphery, can lead to autoimmunity by activating T cells through T cell receptor signaling. However, in order for optimal activation to occur a second signal, termed “costimulation”, has to be delivered by antigen presenting cells to the T cells. Both the T cell receptor and co-stimulatory signals have been specific targets for therapeutic intervention in autoimmune disease. Strategies targeting both the T cell receptor and costimulation will be discussed in detail within the contents of these review articles (Burrows, Miller, and Vandenbark, for targeting TCR-dependent mechanisms; Weinberg and Miller targeting costimulatory molecules). In human autoimmune diseases, such as MS, RA, and inflammatory bowel disease, activated T cells are found within the inflammatory lesions. However, there has been no direct link between an “autoAg” and a specific T cell receptor that is responsible for the development and/or progression for most of these human diseases. Therefore, finding ways to target and suppress T cellspecific immune activation through mechanisms other than blocking, T cell recognition of autoAg will be discussed in 3 of the 6 reviews (Weinberg, Miller, and Bebo). It has long been noted that for several human autoimmune disorders (e.g. RA, SLE, and MS), there is a large increase of female to male cases. In MS and SLE, the ratio is 10:1 female to male. Thus, sex hormones may influence Ag-specific T cell function during and/or after recognition of autoAg. It has also been noted that female patients with relapsing autoimmune disease have far fewer clinical episodes during pregnancy, again suggesting that sex hormones or pregnancy-specific proteins may suppress T cell specific autoimmune responses. Therefore, modulating sex hormones and the use of pregnancy specific proteins/hormones may have important therapeutic implications for future treatment of autoimmune disease. This subject will be reviewed in the article by Bebo. The group of scientists that have been assembled to write these reviews have all worked with the autoimmune model experimental autoimmune encephalomyelitis (EAE), which is an animal model that mimics the clinical signs of MS. Therefore, the majority of these reviews will focus on discoveries made in the EAE model. Immunizing mice with myelin proteins in a strong immune adjuvant induces EAE, and the majority of autoAg specific T cell responses that have been studied to date are CD4 T cell responses. However, activated CD8 T cells are present in the spinal cord and brain lesions of multiple sclerosis patients, therefore, the final chapter of this issue will be devoted to autoantigen recognition of CD8 T cells and their destructive capabilities in autoimmune disease (Goverman).