Antigenic strength controls the generation of antigen-specific IL-10-secreting T regulatory cells

作者：Gabrysova Leona; Wraith David C^*

来源：European Journal of Immunology, 2010, 40(5): 1386-1395.

DOI：10.1002/eji.200940151

• Autoimmunity
• Cytokines
• Rodent
• T cells
• Tolerance

Administration of peptides i.n. induces peripheral tolerance in Tg4 myelin basic protein-specific TCR-Tg mice. This is characterized by the generation of anergic, IL-10-secreting CD4(+) T cells with regulatory IL-10 Treg). Myelin basic protein Ac1-9 peptide analogs, displaying a hierarchy of affinities for H-2 A(u) (Ac1-9[4K] < < [4A] < [4Y]), were used to investigate the mechanisms of tolerance induction, focusing on IL-10 Treg generation. Repeated i.n. administration of the highest affinity peptide, Ac1-9[4Y], provided complete protection against EAE, while i.n. Ac1-9[4A] and Ac1-9[4K] treatment resulted in only partial protection. Ac1-9[4Y] was also the most potent stimulus for IL-10 Treg generation. Although i.n. treatment with Ac1-9[4A] gave rise to IL-10-secreting CD4(+) T cells, the population as a whole was also capable of secreting IFN-gamma after an in vitro recall response to Ac1-9[4A] or [4Y]. In addition to IL-10 production, other facets of tolerance, namely, anergy and suppression (both in vitro and in vivo), were affinity dependent, with i.n. Ac1-9[4Y]-, [4A]- or [4K]-treated CD4(+) T cells being the most, intermediate and least anergic/suppressive, respectively. These findings demonstrate that the generation of IL-10 Treg in vivo is driven by high signal strength.

• 出版日期2010-5