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Crossroads Between Innate and Adaptive Immunity IV pp 27–35Cite as

Tuning Cross-Presentation of Apoptotic T Cells in Immunopathology

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Part of the book series: Advances in Experimental Medicine and Biology ((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.

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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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Authors and Affiliations

  1. Policlinico Umberto I, Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Viale del Policlinico 155, Rome, 00161, Italy

    Vincenzo Barnaba

  2. Istituto Pasteur-Fondazione Cenci Bolognetti, Rome, 00185, Italy

    Vincenzo Barnaba

  3. Fondazione Andrea Cesalpino, Rome, 00187, Italy

    Vincenzo Barnaba

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  1. Vincenzo Barnaba
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Correspondence to Vincenzo Barnaba .

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Editors and Affiliations

  1. College of Medicine, Department Microbiology & Immunology, Drexel University, Queen Lane 2900, Philadelphia, 19129, Pennsylvania, USA

    Peter D. Katsikis

  2. , Laboratory of Cellular Immunology, La Jolla Institute for Allergy and Immun, Athena Circle 9420, La Jolla, 92037, USA

    Stephen P. Schoenberger

  3. Emory Vaccine Center &, Yerkes National Primate Research Center, Emory University, Gatewood Rd. 954, Atlanta, 30329, Georgia, USA

    Bali Pulendran

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Barnaba, V. (2013). Tuning Cross-Presentation of Apoptotic T Cells in Immunopathology. In: Katsikis, P., Schoenberger, S., Pulendran, B. (eds) Crossroads Between Innate and Adaptive Immunity IV. Advances in Experimental Medicine and Biology, vol 785. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6217-0_3

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