γδ T Cells Protect the Liver and Lungs of Mice from Autoimmunity Induced by Scurfy Lymphocytes

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.