Journal
JOURNAL OF IMMUNOLOGY
Volume 196, Issue 4, Pages 1517-1528Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1501774
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Funding
- intramural program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Japan Society for the Promotion of Science Postdoctoral Fellowships
- Nakatomi Foundation
- Sumitomo Life Welfare and Culture Foundation
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gamma delta T cells have been shown to have immunoregulatory functions in several experimental autoimmune models. A mutation of the Foxp3 gene leads to the absence of regulatory T cells (Tregs) and a fatal systemic autoimmune disease in scurfy mice. Transfer of scurfy lymphocytes to RAG deficient (RAG(-/-)) recipients reproduces the inflammatory phenotype of the scurfy donor, including hepatitis and pneumonitis. In this study, we show that TCR alpha(-/-) recipients, which lack alpha beta T cells but have gamma delta T cells and B cells, are significantly protected from the hepatitis and pneumonitis, but not the dermatitis, induced by adoptive transfer of scurfy lymphocytes. Cotransfer of gamma delta T cells, but not B cells, prevented hepatitis and pneumonitis in RAG(-/-) recipients of scurfy lymphocytes. gamma delta T cells in the TCR alpha(-/-) recipients of scurfy cells markedly expanded and expressed a highly activated (CD62L(lo)CD44(hi)) phenotype. The activated gamma delta T cells expressed high levels of CD39 and NKG2D on their cell surface. A high frequency of scurfy T cells in TCR alpha(-/-) recipients produced IL-10, suggesting that gamma delta T cells may enhance suppressor cytokine production from scurfy T cells in TCR alpha(-/-) recipients. This study indicates that gamma delta T cells may contribute to the maintenance of immunological homeostasis by suppressing autoreactive T cells in liver and lung.
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