title: γδ T Cells Protect the Liver and Lungs of Mice from Autoimmunity Induced by Scurfy Lymphocytes.
abstract: γδ 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 TCRα(-/-) recipients, which lack αβ T cells but have γδ 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 γδ T cells, but not B cells, prevented hepatitis and pneumonitis in RAG(-/-) recipients of scurfy lymphocytes. γδ T cells in the TCRα(-/-) recipients of scurfy cells markedly expanded and expressed a highly activated (CD62L(lo)CD44(hi)) phenotype. The activated γδ T cells expressed high levels of CD39 and NKG2D on their cell surface. A high frequency of scurfy T cells in TCRα(-/-) recipients produced IL-10, suggesting that γδ T cells may enhance suppressor cytokine production from scurfy T cells in TCRα(-/-) recipients. This study indicates that γδ T cells may contribute to the maintenance of immunological homeostasis by suppressing autoreactive T cells in liver and lung.
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Ujiie
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 eshevach@niaid.nih.gov.
authors.forename: Ethan M
authors.initials: EM
authors.lastname: Shevach
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D001081:Apyrase / Q000235:genetics; D001327:Autoimmune Diseases / Q000276:immunology / Q000517:prevention & control*; D015551:Autoimmunity; D003872:Dermatitis / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006505:Hepatitis / Q000276:immunology / Q000517:prevention & control; D006706:Homeostasis; D016753:Interleukin-10 / Q000096:biosynthesis; D008099:Liver / Q000276:immunology*; D008168:Lung / Q000276:immunology*; D008213:Lymphocyte Activation; D008810:Mice, Inbred C57BL; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics; D011014:Pneumonia / Q000276:immunology / Q000517:prevention & control; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D055655:NK Cell Lectin-Like Receptor Subfamily K; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D016753:Interleukin-10; D001081:Apyrase; C067869:CD39 antigen