Unlike T cells restricted by major histocompatibility complex (MHC) class Ia or class II molecules, T cells restricted by MHC class I-like molecules demonstrate properties of both innate and adaptive immunity and are therefore considered innate-like lymphocytes (ILLs). ILLs are believed to have immunoregulatory functions, but their roles in autoimmunity and defense against infections remain elu...

Evidence has been accumulating that shows that insulin-dependent diabetes is subject to immunoregulation. To determine whether cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is involved, we injected anti-CTLA-4 mAb into a TCR transgenic model of diabetes at different stages of disease. When injected into young mice, months before they would normally become diabetic, anti-CTLA-4 induced di...

Nonobese diabetic mice spontaneously develop diabetes that is caused by autoimmune cell-mediated destruction of pancreatic beta cells. Here we report that surgical removal of 90% of pancreatic tissue before onset of insulitis induced a long-term diabetes-free condition in nonobese diabetic mice. Pancreatectomy after development of moderate insulitis had no effect on the course of diabetes. The ...

The mechanisms by which cytotoxic T lymphocytes (CTLs) enter and are retained in nonlymphoid tissue are not well characterized. With a transgenic mouse expressing the NKG2D ligand retinoic acid early transcript 1ε (RAE1ε) in β-islet cells of the pancreas, we found that RAE1 expression was sufficient to induce the recruitment of adoptively transferred CTLs to islets. This was dependent on NKG2D ...

Diabetes-prone BioBreeding/Worcester (BB/Wor) rats received thrice weekly injections of mAb against antigens expressed on the surface of all T cells (OX19), cytotoxic/suppressor, and NK cells (OX8), helper/inducer cells (W3/25, OX35, OX38), and Ia+ cells (OX6, 3JP, OX17). Treatment with OX8 or OX19 achieved stable reductions of splenic and peripheral blood NK cells and helper/inducer T lymphocy...

Type 1A diabetes (T1D) is an autoimmune disease characterized by leukocyte infiltration of the pancreatic islets of Langerhans. A major impediment to advances in understanding, preventing, and curing T1D has been the inability to "see" the disease initiate, progress, or regress, especially during the occult phase. Here, we report the development of a noninvasive method to visualize T1D at the t...

The nonobese diabetic (NOD) mouse strain provides a model system for human autoimmune diabetes. This disease model is extensively used not only to examine the etiology and pathogenesis of diabetes, but also as a means to evaluate therapies. In NOD mice, the disease progresses from insulitis to islet destruction and clinical diabetes in a high percentage of female mice. In this study, androgen t...

the biobreeding- diabetes prone (bb-dp) rat spontaneously develops an autoimmune diabetic syndrome that is dependent on the rt1 u major histocompatibility complex (mhc) haplotype and homozygosity for an allele at the lymphopenia (lyp) locus. lyp mutation is responsible for a peripheral t -lymphopenia. there are other genetic loci contributing to diabetes susceptibility in this strain. bb rats c...