期刊
JOURNAL OF IMMUNOLOGY
卷 195, 期 12, 页码 5572-5581出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1501604
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资金
- National Institutes of Health [R01EY021199, T32AI007405]
- Department of Breast and Thyroid Surgery, Tongyi Hospital, Wuhan City, People's Republic of China
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 gamma delta T cells, such that similar to 80% of female B10.TCR delta(-/-) mice develop keratitis by 18 wk of age. In this article, we show that CD8(+) alpha beta T cells are the drivers of this disease, because adoptive transfer of CD8(+), but not CD4(+), T cells to keratitis-resistant B10. TCR beta/delta(-/-) hosts induced a high incidence of keratitis. This finding was unexpected because in other autoimmune diseases, more often CD4+ alpha beta T cells, or both CD4+ and CD8+ alpha beta T cells, mediate the disease. Compared with wild-type B10 mice, B10. TCR beta/delta(-/-) mice also show increased percentages of peripheral memory phenotype CD8(+) alpha beta T cells, along with an elevated frequency of CD8(+) alpha beta T cells biased to produce inflammatory cytokines. In addition, B10.TCR delta(-/-) mice have fewer peripheral CD4(+) CD25(+) Foxp3(+) alpha beta 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, gamma delta T cells are required to generate adequate numbers of CD4(+) CD25(+) Foxp3(+) Tregs, and that in B10. TCR beta/delta(-/-) mice a Treg deficiency allows dysregulated effector or memory CD8(+) alpha beta T cells to infiltrate the cornea and provoke an autoimmune attack.
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