Tregs in T cell vaccination: exploring the regulation of regulation
Irun R. Cohen, … , Francisco J. Quintana, Avishai Mimran
Irun R. Cohen, … , Francisco J. Quintana, Avishai Mimran
Published November 1, 2004
Citation Information: J Clin Invest. 2004;114(9):1227-1232. https://doi.org/10.1172/JCI23396.
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Review Series

Tregs in T cell vaccination: exploring the regulation of regulation

Abstract

T cell vaccination (TCV) activates Tregs of 2 kinds: anti-idiotypic (anti-id) and anti-ergotypic (anti-erg). These regulators furnish a useful view of the physiology of T cell regulation of the immune response. Anti-id Tregs recognize specific effector clones by their unique TCR CDR3 peptides; anti-id networks of CD4+ and CD8+ Tregs have been described in detail. Here we shall focus on anti-erg T regulators. Anti-erg T cells, unlike anti-id T cells, do not recognize the clonal identity of effector T cells; rather, anti-erg T cells recognize the state of activation of target effector T cells, irrespective of their TCR specificity. We consider several features of anti-erg T cells: their ontogeny, subset markers, and target ergotope molecules; mechanisms by which they regulate other T cells; mechanisms by which they get regulated; and therapeutic prospects for anti-erg upregulation and downregulation.

Authors

Irun R. Cohen, Francisco J. Quintana, Avishai Mimran

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Figure 1

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The balance between Treg loss (red arrows) and Treg renewal (green arrow...
The balance between Treg loss (red arrows) and Treg renewal (green arrows). Resting Tregs can be activated by recognizing a specific ergotope presented in either of 2 ways: by an activated effector T cell or by a professional APC (yellow cell). The interaction between the activated Treg (green cells) and the activated effector T cell (purple cells) leads to inactivation of the effector T cell but also to anergy of the Treg (white cells). Thus, presentation of ergotopes by activated T cells leads to Treg loss. In contrast, an ergotope presented by a professional APC activates Treg proliferation and cycling (Treg renewal).