γδ T cells are essential effectors of type 1 diabetes in the nonobese diabetic mouse model

Janet G.M. Markle, Steve Mortin-Toth, Andrea S.L. Wong, Liping Geng, Adrian Hayday, Jayne S. Danska

Research output: Contribution to journalArticlepeer-review

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-CD44hi and CD27+CD44lo subsets, infiltrate islets of prediabetic NOD mice. Moreover, NOD CD27-CD44hi and CD27 +CD44lo 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.

Original languageEnglish (US)
Pages (from-to)5392-5401
Number of pages10
JournalJournal of Immunology
Volume190
Issue number11
DOIs
StatePublished - Jun 1 2013
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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