Induction of peripheral T cell tolerance by antigen-presenting B cells. I. Relevance of antigen presentation persistence.
Various mechanisms of peripheral T cell tolerization have evolved to avoid responses mediated by autoreactive T cells that have not been eliminated in the thymus. In this study, we investigated the peripheral conditions of Ag presentation required to induce T cell tolerance when the predominant APCs are B cells. We show that transient Ag presentation, in absence of inflammation and in a self-context, induces CD4(+) T cell activation and memory formation. In contrast, chronic Ag presentation leads to CD4(+) T cell tolerance. The importance of long-lasting Ag presentation in inducing tolerance was also confirmed in the herpes stromal keratitis autoimmune disease model. Keratogenic T cells could be activated or tolerized depending on the APC short or long persistence. Thus, when APCs are B cells, the persistence of the Ag presentation itself is one of the main conditions to have peripheral T cell tolerance.
Department of Biotechnology and Bioscience, University of Milano-Bicocca, Italy.
Giorgio
G
Raimondi
Ivan
I
Zanoni
Stefania
S
Citterio
Paola
P
Ricciardi-Castagnoli
Francesca
F
Granucci
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D006564:Herpesviridae / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology; D016849:Keratitis, Herpetic / Q000276:immunology; D007700:Kinetics; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology*