title: γδ T cells are essential effectors of type 1 diabetes in the nonobese diabetic mouse model.
abstract: γδ T cells, a lineage of innate-like lymphocytes, are distinguished from conventional αβ T cells in their Ag recognition, cell activation requirements, and effector functions. γδ T cells have been implicated in the pathology of several human autoimmune and inflammatory diseases and their corresponding mouse models, but their specific roles in these diseases have not been elucidated. We report that γδ TCR(+) cells, including both the CD27(-)CD44(hi) and CD27(+)CD44(lo) subsets, infiltrate islets of prediabetic NOD mice. Moreover, NOD CD27(-)CD44(hi) and CD27(+)CD44(lo) γδ T cells were preprogrammed to secrete IL-17, or IFN-γ upon activation. Adoptive transfer of type 1 diabetes (T1D) to T and B lymphocyte-deficient NOD recipients was greatly potentiated when γδ T cells, and specifically the CD27(-) γδ T cell subset, were included compared with transfer of αβ T cells alone. Ab-mediated blockade of IL-17 prevented T1D transfer in this setting. Moreover, introgression of genetic Tcrd deficiency onto the NOD background provided robust T1D protection, supporting a nonredundant, pathogenic role of γδ T cells in this model. The potent contributions of CD27(-) γδ T cells and IL-17 to islet inflammation and diabetes reported in this study suggest that these mechanisms may also underlie human T1D.
authors.affiliation: Programme in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario MG5 1L7, Canada.
authors.forename: Janet G M
authors.initials: JG
authors.lastname: Markle
authors.forename: Steve
authors.initials: S
authors.lastname: Mortin-Toth
authors.forename: Andrea S L
authors.initials: AS
authors.lastname: Wong
authors.forename: Liping
authors.initials: L
authors.lastname: Geng
authors.forename: Adrian
authors.initials: A
authors.lastname: Hayday
authors.forename: Jayne S
authors.initials: JS
authors.lastname: Danska
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D018628:Gene Dosage; D005838:Genotype; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism
chemical_list: D018960:Hyaluronan Receptors; D020381:Interleukin-17; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7