| First Author | Markle JG | Year | 2013 |
| Journal | J Immunol | Volume | 190 |
| Issue | 11 | Pages | 5392-401 |
| PubMed ID | 23626013 | Mgi Jnum | J:195691 |
| Mgi Id | MGI:5485039 | Doi | 10.4049/jimmunol.1203502 |
| Citation | Markle JG, et al. (2013) gammadelta T cells are essential effectors of type 1 diabetes in the nonobese diabetic mouse model. J Immunol 190(11):5392-401 |
| abstractText | gammadelta T cells, a lineage of innate-like lymphocytes, are distinguished from conventional alphabeta T cells in their Ag recognition, cell activation requirements, and effector functions. gammadelta 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 gammadelta 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) gammadelta T cells were preprogrammed to secrete IL-17, or IFN-gamma upon activation. Adoptive transfer of type 1 diabetes (T1D) to T and B lymphocyte-deficient NOD recipients was greatly potentiated when gammadelta T cells, and specifically the CD27(-) gammadelta T cell subset, were included compared with transfer of alphabeta 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 gammadelta T cells in this model. The potent contributions of CD27(-) gammadelta T cells and IL-17 to islet inflammation and diabetes reported in this study suggest that these mechanisms may also underlie human T1D. |
