title: T cell anergy as a strategy to reduce the risk of autoimmunity.
abstract: Some self-reactive immature T cells escape negative selection in the thymus and may cause autoimmune diseases later. In the periphery, if T cells are stimulated insufficiently by peptide-major histocompatibility complex, they become inactive and their production of cytokines changes, a phenomenon called "T cell anergy". In this paper, we explore the hypothesis that T cell anergy may function to reduce the risk of autoimmunity. The underlying logic is as follows: Since those self-reactive T cells that receive strong stimuli from self-antigens are eliminated in the thymus, T cells that receive strong stimuli in the periphery are likely to be non-self-reactive. As a consequence, when a T cell receives a weak stimulus, the likelihood that the cell is self-reactive is higher than in the case that it receives a strong stimulus. Therefore, inactivation of the T cell may reduce the danger of autoimmunity. We consider the formalism in which each T cell chooses its response depending on the strength of stimuli in order to reduce the risk of autoimmune diseases while maintaining its ability to attack non-self-antigens effectively. The optimal T cell responses to a weak and a strong stimulus are obtained both when the cells respond in a deterministic manner and when they respond in a probabilistic manner. We conclude that T cell anergy is the optimal response when a T cell meets with antigen-presenting cells many times in its lifetime, and when the product of the autoimmunity risk and the number of self-reactive T cells has an intermediate value.
authors.affiliation: Department of Biology, Faculty of Sciences, Kyushu University, Fukuoka 812-8581, Japan. saekikou@bio-math10.biology.kyushu-u.ac.jp
authors.forename: Koichi
authors.initials: K
authors.lastname: Saeki
authors.forename: Yoh
authors.initials: Y
authors.lastname: Iwasa
mesh_terms: D015551:Autoimmunity / Q000276:immunology*; D017635:Clonal Anergy / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D018448:Models, Immunological; D012307:Risk Factors; D013601:T-Lymphocytes / Q000276:immunology*