An Islet-Specific Pulse of TGF-{beta} Abrogates CTL Function and Promotes {beta} Cell Survival Independent of Foxp3+ T Cells

Maja Wållberg, F Susan Wong, E Allison Green

Research output: Contribution to journalArticlepeer-review

Abstract

Effective therapies that prevent chronic inflammation from developing into type 1 diabetes remain elusive. In this study, we show that expression of TGF-ß for just 1 wk in inflamed islets of NOD mice significantly delays diabetes development. Time course studies demonstrated that the brief TGF-ß pulse protects only if administered when extensive ß cell destruction has occurred. Surprisingly, TGF-ß-mediated protection is not linked to enhanced Foxp3(+) regulatory T cell activity or to decreased intrapancreatic presentation of islet Ags. Instead, TGF-ß disables the transition of primed autoreactive CD8(+) T cells to cytotoxic effectors and decreases generation, or maintenance, of CD8(+) memory T cells within the pancreas, significantly impairing their diabetogenic capacity.
Original languageEnglish
Pages (from-to)2543-2551
Number of pages9
JournalJournal of Immunology
Volume186
Issue number4
DOIs
Publication statusPublished - 15 Feb 2011

Cite this