TY - JOUR
T1 - An Islet-Specific Pulse of TGF-{beta} Abrogates CTL Function and Promotes {beta} Cell Survival Independent of Foxp3+ T Cells
AU - Wållberg, Maja
AU - Wong, F Susan
AU - Green, E Allison
PY - 2011/2/15
Y1 - 2011/2/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79951847399&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1002098
DO - 10.4049/jimmunol.1002098
M3 - Article
C2 - 21217013
SN - 0022-1767
VL - 186
SP - 2543
EP - 2551
JO - Journal of Immunology
JF - Journal of Immunology
IS - 4
ER -