Autoimmunity: The good, the bad, and the ugly.

Abstract

Some readers may remember, as I do, that we were taught to consider autoimmunity as the result of an imbalance of the immune system, often with bad or ugly (translation: very bad) consequences, including refractoriness to treatment, irreversible deficits, or death. We now know that there is protective (good) autoimmunity that can prevent the development of disease, at least in animal models. Indeed, an article by Ortega et al.1 shows that, depending on the type of antigen and mouse strain, it is possible to generate CD8+ T cells that suppress the development of experimental autoimmune encephalitis (EAE). The authors had previously reported this protective effect in C57BL/6 mice showing that MOG35-55-specific CD8+ T cells suppressed EAE development. In the current article, they demonstrate that using other myelin peptides, such as PLP178-191 and other susceptible mouse strains (SJL), the generated myelin-specific CD8+ T cells were able to suppress disease. The disease-preventing function of these cells was dependent on the specific cognate myelin antigen. Moreover, the generation of the T cells depended on the presence of both CD4+ and CD8+ T-cell epitopes in the antigen used to immunize the mice, and did not appear to be affected by thymic selection. Findings from these models improve our understanding of autoregulatory CD8+ T cells, and have implications for the development of novel therapies for immune-mediated diseases. In contrast, most common treatment approaches to autoimmune disorders use drugs that rebalance the abnormal immune response toward suppressive mechanisms. Molnarfi et al.2 show in another article in this issue that glatiramer acetate inhibits the type I interferon (IFN) pathway in monocyte type II (M2) polarization.