B-cells promote intra-islet CD8+ cytotoxic T-cell survival to enhance type 1 diabetes

Gillian M Brodie, Maja Wallberg, Pere Santamaria, F Susan Wong, E Allison Green

Research output: Contribution to journalArticlepeer-review

Abstract

To determine the role of B-cells in promoting CD8(+) T-cell-mediated beta cell destruction in chronically inflamed islets. RESEARCH DESIGN AND METHODS-RIP: TNFalpha-NOD mice were crossed to B-cell-deficient NOD mice, and diabetes development was monitored. We used in vitro antigen presentation assays and in vivo administration of bromodeoxyuridine coupled to flow cytometry assays to assess intra-islet T-cell activation in the absence or presence of B-cells. CD4(+)Foxp3(+) activity in the absence or presence of B-cells was tested using in vivo depletion techniques. Cytokine production and apoptosis assays determined the capacity of CD8(+) T-cells transform to cytotoxic T-lymphocytes (CTLs) and survive within inflamed islets in the absence or presence of B-cells.
Original languageEnglish
Pages (from-to)909-17
Number of pages9
JournalDiabetes
Volume57
Issue number4
DOIs
Publication statusPublished - Apr 2008

Keywords

  • Animals
  • Antigen-Presenting Cells
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Cell Survival
  • Cytokines
  • Diabetes Mellitus, Type 1
  • Inflammation
  • Insulin-Secreting Cells
  • Lymphocyte Depletion
  • Mice
  • Mice, Inbred NOD

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