?? T Cell-Dependent Regulatory T Cells Prevent the Development of Autoimmune Keratitis.

ABSTRACT: To prevent potentially damaging inflammatory responses, the eye actively promotes local immune tolerance via a variety of mechanisms. Owing to trauma, infection, or other ongoing autoimmunity, these mechanisms sometimes fail, and an autoimmune disorder may develop in the eye. In mice of the C57BL/10 (B10) background, autoimmune keratitis often develops spontaneously, particularly in the females. Its incidence is greatly elevated in the absence of ?? T cells, such that ?80% of female B10.TCR?(-/-) mice develop keratitis by 18 wk of age. In this article, we show that CD8(+) ?? T cells are the drivers of this disease, because adoptive transfer of CD8(+), but not CD4(+), T cells to keratitis-resistant B10.TCR?/?(-/-) hosts induced a high incidence of keratitis. This finding was unexpected because in other autoimmune diseases, more often CD4(+) ?? T cells, or both CD4(+) and CD8(+) ?? T cells, mediate the disease. Compared with wild-type B10 mice, B10.TCR?(-/-) mice also show increased percentages of peripheral memory phenotype CD8(+) ?? T cells, along with an elevated frequency of CD8(+) ?? T cells biased to produce inflammatory cytokines. In addition, B10.TCR?-/- mice have fewer peripheral CD4(+) CD25(+) Foxp3(+) ?? regulatory T cells (Tregs), which express lower levels of receptors needed for Treg development and function. Together, these observations suggest that in B10 background mice, ?? T cells are required to generate adequate numbers of CD4(+) CD25(+) Foxp3(+) Tregs, and that in B10.TCR?(-/-) mice a Treg deficiency allows dysregulated effector or memory CD8(+) ?? T cells to infiltrate the cornea and provoke an autoimmune attack.

SUBMITTER: Huang Y 

PROVIDER: S-EPMC4670787 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature