NKG2D is implicated in autoimmune diabetes. However, the role of this receptor
in diabetes pathogenesis is unclear owing to conflicting results with studies
involving global inhibition of NKG2D signaling. We found that NKG2D and its
ligands are present in human pancreata, with expression of NKG2D and its
ligands increased in the islets of patients with type 1 diabetes. To directly
assess the role of NKG2D in the pancreas, we generated NOD mice that express an
NKG2D ligand in b-islet cells. Diabetes
was reduced in these mice. The reduction corresponded with a decrease in the effector
to central memory CD8<sup>+</sup> T cell ratio. Further, NKG2D signaling during in vitro activation of both
mouse and human CD8+ T cells resulted in an increased number of central
memory CD8<sup>+</sup> T cells
and diabetes protection by central memory CD8<sup>+</sup> T cells in
vivo. Taken together, these studies demonstrate that there is a protective role
for central memory CD8<sup>+</sup> T cells in autoimmune diabetes and that this
protection is enhanced with NKG2D signaling.
These findings stress the
importance of anatomical location when determining the role NKG2D signaling
plays, as well as when developing therapeutic strategies targeting this
pathway, in type 1 diabetes development.
Role of IL28B Gene Polymorphism and Cell-Mediated Immunity in Spontaneous Resolution of Acute Hepatitis C
