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Antigenic strength controls the generation of antigen‐specific IL‐10‐secreting T regulatory cells
Author(s) -
Gabryšová Leona,
Wraith David C.
Publication year - 2010
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.200940151
Subject(s) - biology , immunology , antigen , myelin basic protein , immune tolerance , population , microbiology and biotechnology , in vivo , myelin , medicine , endocrinology , genetics , environmental health , central nervous system
Abstract 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 function (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‐γ 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.