Arthritogenic Self-reactive CD4+ T Cells Acquire an FR4hiCD73hi Anergic State in the Presence of Foxp3+ Regulatory T Cells

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2011 Nov 30

PMID 22124124

Citations 68

Authors

Ryan J Martinez

Na Zhang

Stephanie R Thomas

Sarada L Nandiwada

Marc K Jenkins

Bryce A Binstadt

Daniel L Mueller

Affiliations

Soon will be listed here.

Abstract

Rheumatoid arthritis develops in association with a defect in peripheral CD4(+) T cell homeostasis. T cell lymphopenia has also been shown to be a barrier to CD4(+) T cell clonal anergy induction. We therefore explored the relationship between clonal anergy induction and the avoidance of autoimmune arthritis by tracking the fate of glucose-6-phosphate isomerase (GPI)-reactive CD4(+) T cells in the setting of selective T cell lymphopenia. CD4(+) T cell recognition of self-GPI peptide/MHC class II complexes in normal murine hosts did not lead to arthritis and instead caused those T cells to develop a Folate receptor 4(hi)CD73(hi) anergic phenotype. In contrast, hosts selectively depleted of polyclonal Foxp3(+)CD4(+) regulatory T cells could not make GPI-specific CD4(+) T cells anergic and failed to control arthritis. This suggests that autoimmune arthritis develops in the setting of lymphopenia when Foxp3(+)CD4(+) regulatory T cells are insufficient to functionally inactivate all autoreactive CD4(+) T cells that encounter self-Ag.

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