Tolerogenic vaccines: Targeting the antigenic and cytokine niches of FOXP3 + regulatory T cells.

Autor: Mannie MD; Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, United States. Electronic address: manniem@ecu.edu., DeOca KB; Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, United States., Bastian AG; Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, United States., Moorman CD; Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, United States.
Jazyk: angličtina
Zdroj: Cellular immunology [Cell Immunol] 2020 Sep; Vol. 355, pp. 104173. Date of Electronic Publication: 2020 Jul 15.
DOI: 10.1016/j.cellimm.2020.104173
Abstrakt: FOXP3 + regulatory T cells (Tregs) constitute a critical barrier that enforces tolerance to both the self-peptidome and the extended-self peptidome to ensure tissue-specific resistance to autoimmune, allergic, and other inflammatory disorders. Here, we review intuitive models regarding how T cell antigen receptor (TCR) specificity and antigen recognition efficiency shape the Treg and conventional T cell (Tcon) repertoires to adaptively regulate T cell maintenance, tissue-residency, phenotypic stability, and immune function in peripheral tissues. Three zones of TCR recognition efficiency are considered, including Tcon recognition of specific low-efficiency self MHC-ligands, Treg recognition of intermediate-efficiency agonistic self MHC-ligands, and Tcon recognition of cross-reactive high-efficiency agonistic foreign MHC-ligands. These respective zones of TCR recognition efficiency are key to understanding how tissue-resident immune networks integrate the antigenic complexity of local environments to provide adaptive decisions setting the balance of suppressive and immunogenic responses. Importantly, deficiencies in the Treg repertoire appear to be an important cause of chronic inflammatory disease. Deficiencies may include global deficiencies in Treg numbers or function, subtle 'holes in the Treg repertoire' in tissue-resident Treg populations, or simply Treg insufficiencies that are unable to counter an overwhelming molecular mimicry stimulus. Tolerogenic vaccination and Treg-based immunotherapy are two therapeutic modalities meant to restore dominance of Treg networks to reverse chronic inflammatory disease. Studies of these therapeutic modalities in a preclinical setting have provided insight into the Treg niche, including the concept that intermediate-efficiency TCR signaling, high IFN-β concentrations, and low IL-2 concentrations favor Treg responses and active dominant mechanisms of immune tolerance. Overall, the purpose here is to assimilate new and established concepts regarding how cognate TCR specificity of the Treg repertoire and the contingent cytokine networks provide a foundation for understanding Treg suppressive strategy.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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