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

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 γδ T cells, such that ∼80% of female B10.TCRδ(-/-) mice develop keratitis by 18 wk of age. In this article, we show that CD8(+) αß T cells are the drivers of this disease, because adoptive transfer of CD8(+), but not CD4(+), T cells to keratitis-resistant B10.TCRß/δ(-/-) hosts induced a high incidence of keratitis. This finding was unexpected because in other autoimmune diseases, more often CD4(+) αß T cells, or both CD4(+) and CD8(+) αß T cells, mediate the disease. Compared with wild-type B10 mice, B10.TCRδ(-/-) mice also show increased percentages of peripheral memory phenotype CD8(+) αß T cells, along with an elevated frequency of CD8(+) αß T cells biased to produce inflammatory cytokines. In addition, B10.TCRδ-/- mice have fewer peripheral CD4(+) CD25(+) Foxp3(+) αß 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, γδ T cells are required to generate adequate numbers of CD4(+) CD25(+) Foxp3(+) Tregs, and that in B10.TCRδ(-/-) mice a Treg deficiency allows dysregulated effector or memory CD8(+) αß T cells to infiltrate the cornea and provoke an autoimmune attack.

Regulation of IgE Responses by γδ T Cells.

Immunoglobulin E (IgE) antibodies play a crucial role in host defense against parasite infections. However, inappropriate IgE responses are also involved in the pathogenesis of allergic diseases. The generation of IgE antibodies is a tightly controlled process regulated by multiple transcription factors, cytokines, and immune cells including γδ T cells. Accumulating evidence demonstrates that γδ T cells play a critical role in regulating IgE responses; however, both IgE-enhancing and IgE-suppressive effects are suggested for these cells in different experimental systems. In this review, we examine the available evidence and discuss the role of γδ T cells in IgE regulation both in the context of antigen-induced immune responses and in the state of partial immunodeficiency.