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Tuning Cross-Presentation of Apoptotic T Cells in Immunopathology

  • Vincenzo BarnabaEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 785)

Abstract

Cross-presentation of several long-lived antigens associated with apoptotic T cells requires caspase-dependent cleavage to efficiently deliver antigenic fragments to the processing machinery of antigen-presenting cells. The resulting emergence of a large population of autoreactive CD8+ T effector cells specific for apoptotic T cell-associated self-epitopes plays a key role in improving immunopathology in several infections and autoimmune diseases. Importantly, they endow mixed polyfunctional type-1, type-2, and type-17 responses and correlate with the chronic progression of various pathological conditions. This evolution is related to the selection of autoreactive CD8+ T cells with higher T cell receptor avidity, whereas those with lower avidity undergo prompt contraction in patients undergoing disease resolution. The development of mixed responses with divergent differentiation requirements is consistent with distinct sites or kinetics of CD8+ T cell priming in vivo. Therefore, we propose a strict link among cross-presentation of apoptotic T cells, the generation of high frequencies of mixed autoreactive CD8+ T cells producing a broad array of cytokines (IFN-γ, IL-17, IL-4, IL-2, etc.), and the progression towards chronic inflammatory diseases.

Keywords

Cross-presentation Apoptotic T cells Apoptotic epitope-specific CD8+ T cells 

Notes

Acknowledgments

This work was supported by the following: European Union grants (IMECS n. 201169, FP7-Health-2007-A and SPHYNX n. 261365, FP7-Health-2010); Ministero della Sanità (Ricerca finalizzata [RFPS-2006-3-337923 and RFPS-2007-1-636647]; Istituto Superiore di Sanità [Progetto AIDS-2006 and -2008]); Ministero dell’Istruzione, dell’Università e della Ricerca (MIUR) (Programmi di ricerca di interesse nazionale [PRIN]-2008/10 n. 7245/1; Fondo per gli investimenti di ricerca di base [FIRB]-2011/13 n. RBAP10TPXK); Fondazione Cariplo (progetti n. 13535 and 3603 2010/12); and Associazione Italiana per la Ricerca sul Cancro (AIRC) (progetto “Investigator Grant” [IG]-2010/13 n. 10756).

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Policlinico Umberto I, Dipartimento di Medicina Interna e Specialità MedicheSapienza Università di RomaRomeItaly
  2. 2.Istituto Pasteur-Fondazione Cenci BolognettiRomeItaly
  3. 3.Fondazione Andrea CesalpinoRomeItaly

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