Induction of peripheral T cell tolerance by antigen-presenting B cells. II. Chronic antigen presentation overrules antigen-presenting B cell activation.
Ag presentation in the absence of danger signals and Ag persistence are the inductive processes of peripheral T cell tolerization proposed so far. Nevertheless, it has never been definitively shown that chronic Ag presentation per se can induce T cell tolerance independent of the state of activation of APCs. In the present work, we investigated whether chronic Ag presentation by either resting or activated B cells can induce tolerance of peripheral Ag-specific T cells. We show that CD4(+) T cells that re-encounter the Ag for a prolonged period, presented either by resting or activated Ag-presenting B cells, become nonfunctional and lose any autoimmune reactivity. Thus, when the main APCs are B cells, the major mechanism responsible for peripheral T cell tolerization is persistent Ag exposure, independent of the B cell activation state.
Department of Biotechnology and Bioscience, University of Milano-Bicocca, Milan, 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 / Q000166:cytology* / Q000276:immunology*; D015415:Biomarkers; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology*
D015415:Biomarkers