Arthritogenic self-reactive CD4+ T cells acquire an FR4hiCD73hi anergic state in the presence of Foxp3+ regulatory T cells

RJ Martinez, N Zhang, SR Thomas… - The Journal of …, 2012 - journals.aai.org
RJ Martinez, N Zhang, SR Thomas, SL Nandiwada, MK Jenkins, BA Binstadt, DL Mueller
The Journal of Immunology, 2012journals.aai.org
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 …
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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