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Cbl-b deficiency prevents functional but not phenotypic T cell anergy

Authors :
Walter L. Eckalbar
Trang Nguyen
Lin Shen
Zhi-En Wang
Arthur Weiss
Andrew Schroeder
Source :
The Journal of Experimental Medicine
Publication Year :
2021
Publisher :
Rockefeller University Press, 2021.

Abstract

T cell anergy is an important peripheral tolerance mechanism to prevent autoimmunity. Nguyen et al. find that T cell anergy develops in the periphery, not in the thymus, and depends upon Cbl-b but not Grail or PD-1.<br />T cell anergy is an important peripheral tolerance mechanism. We studied how T cell anergy is established using an anergy model in which the Zap70 hypermorphic mutant W131A is coexpressed with the OTII TCR transgene (W131AOTII). Anergy was established in the periphery, not in the thymus. Contrary to enriched tolerance gene signatures and impaired TCR signaling in mature peripheral CD4 T cells, CD4SP thymocytes exhibited normal TCR signaling in W131AOTII mice. Importantly, the maintenance of T cell anergy in W131AOTII mice required antigen presentation via MHC-II. We investigated the functional importance of the inhibitory receptor PD-1 and the E3 ubiquitin ligases Cbl-b and Grail in this model. Deletion of each did not affect expression of phenotypic markers of anergic T cells or T reg numbers. However, deletion of Cbl-b, but not Grail or PD-1, in W131AOTII mice restored T cell responsiveness and signaling. Thus, Cbl-b plays an essential role in the establishment and/or maintenance of unresponsiveness in T cell anergy.<br />Graphical Abstract

Details

ISSN :
15409538 and 00221007
Volume :
218
Database :
OpenAIRE
Journal :
Journal of Experimental Medicine
Accession number :
edsair.doi.dedup.....40f5d93f06bacf69b0157c3a6c09db4e
Full Text :
https://doi.org/10.1084/jem.20202477