Regulatory T Cells Maintain Selective Access to IL-2 and Immune Homeostasis Despite Substantially Reduced CD25 Function

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2020 Oct 15

PMID 33055282

Citations 15

Authors

Erika T Hayes

Cassidy E Hagan

Liliane Khoryati

Marc A Gavin

Daniel J Campbell

Affiliations

Soon will be listed here.

Abstract

IL-2 is a critical regulator of immune homeostasis through its impact on both regulatory T (Treg) and effector T cells. However, the precise role of IL-2 in the maintenance and function of Treg cells in the adult peripheral immune system remains unclear. In this study, we report that neutralization of IL-2 in mice abrogated all IL-2R signaling in Treg cells, but was well tolerated and only gradually impacted Treg cell function and immune homeostasis. By contrast, despite substantially reduced IL-2 sensitivity, Treg cells maintained selective IL-2 signaling and prevented immune dysregulation following treatment with the inhibitory anti-CD25 Ab PC61. Reduction of Treg cells with a depleting version of the same CD25 Ab permitted CD8 effector T cell proliferation before progressing to more widespread immune dysregulation. Thus, despite severely curtailed CD25 expression and function, Treg cells retain selective access to IL-2 that supports their anti-inflammatory functions in vivo. Ab-mediated targeting of CD25 is being actively pursued for treatment of autoimmune disease and prevention of allograft rejection, and our findings help inform therapeutic manipulation and design for optimal patient outcomes.

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