Overproduction of IL-2 by Cbl-b deficient CD4+ T cells provides resistance against regulatory T cells. (1st January 2020)

• Record Type: Journal Article
• Authors: Han, SeongJun; Chung, Douglas C.; St. Paul, Michael; Liu, Zhe Qi; Garcia-Batres, Carlos; Elford, Alisha R.; Tran, Charles W.; Chapatte, Laurence; Ohashi, Pamela S.
• Is Part Of: Oncoimmunology. Volume 9:Number 1(2020)
• Publication Date: 2020-01-01
• Subjects: Immune regulation -- T cell -- Treg -- cytokine; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2020.1737368
• Languages: English
• ISSNs: 2162-402X

Abstract

ABSTRACT: Regulatory T cells are integral to the regulation of autoimmune and anti-tumor immune responses. However, several studies have suggested that changes in T cell signaling networks can result in T cells that are resistant to the suppressive effects of regulatory T cells. Here, we investigated the role of Cbl-b, an E3 ubiquitin ligase, in establishing resistance to Treg-mediated suppression. We found that the absence of Cbl-b, a negative regulator of multiple TCR signaling pathways, rendered T cells impartial to Treg suppression by regulating cytokine networks leading to improved anti-tumor immunity despite the presence of Treg cells in the tumor. Specifically, Cbl-b KO CD4 + FoxP3 − T cells hyper-produced IL-2 and together with IL-2 Rα upregulation served as an essential mechanism to escape suppression by Treg cells. Furthermore, we report that IL-2 serves as the central molecule required for cytokine-induced Treg resistance. Collectively our data emphasize the role of IL-2 as a key mechanism that renders CD4 + T cells resistant to the inhibitory effects of Treg cells.