Arthritogenic Self-Reactive CD4(+) T Cells Acquire an FR4(hi) CD73(hi) Anergic State in the Presence of Foxp3(+) Regulatory T Cells

作者：Martinez Ryan J; Zhang Na; Thomas Stephanie R; Nandiwada Sarada L; Jenkins Marc K; Binstadt Bryce A; Mueller Daniel L^*

来源：The Journal of Immunology, 2012, 188(1): 170-181.

DOI：10.4049/jimmunol.1101311

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 selfAg. The Journal of Immunology, 2012, 188: 170-181.

• 出版日期2012-1-1