Arthritogenic self-reactive CD4 + T cells acquire an FR4 hiCD73 hi anergic state in the presence of foxp3 + regulatory t cells

Ryan J. Martinez, Na Zhang, Stephanie R. Thomas, Sarada L. Nandiwada, Marc Jenkins, Bryce A Binstadt, Daniel L Mueller

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


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 hiCD73 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.

Original languageEnglish (US)
Pages (from-to)170-181
Number of pages12
JournalJournal of Immunology
Issue number1
StatePublished - Jan 1 2012


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