The use of haploidentical, gender-matched, predisposing T1DM genotype-free HSCs in combination with MHC-disparate MSCs could lead to the development of a safe protocol for the induction of hematopoietic chimerism for the treatment of T1DM.
We investigated MHC-II-mediated protection from type 1 diabetes using a previously reported NOD mouse line expressing an Eα transgene and, thereby, the Eα:Eβ complex.
The presence of IFNα/β is correlated with characteristic MHC class I (MHC-I) hyperexpression found in the islets of patients with T1D, suggesting that T1-IFNs modulate the cross-talk between autoreactive cytotoxic CD8<sup>+</sup> T lymphocytes and insulin-producing pancreatic β cells.
Our results suggest that the interaction of KIRs with HLA-C ligands are significant and certain combinations contribute to susceptibility to and protection against Type 1 diabetes.
In the mouse model of T1D, CD4 T cells respond to insulin B-chain peptide (B:9-23) mimotopes engineered to bind the mouse MHCII molecule, IA(g7), in an unfavorable position or register.
Antigen-presenting cell-associated four-domain MHC class II (MHC-II) molecules play a central role in activating autoreactive CD4(+) T cells involved in multiple sclerosis (MS) and type 1 diabetes (T1D).
Children with type 1 diabetes who were positive for KIR2DS2/KIR2DL2 and KIR2DL3 were more often homozygous for HLA-C group 1 and this effect was strongest in children diagnosed with diabetes before the age of 5 years (p = 0.003, corrected p [p (corr)] = 0.012) and (p = 0.001, p (corr) = 0.004), respectively.
Non-MHC genes associated with susceptibility to type 1 diabetes in both Japanese and Caucasoid patients include polymorphisms in the insulin gene, the cytotoxic T-lymphocyte antigen 4 (CTLA4) gene, the interleukin-18 (IL18) gene and the major histocompatibility complex class I chain-related gene A (MICA) gene.
Recent studies have established that disease concordance in dizygotic twins is the same as that in siblings generally, for both T1D and the MHC-associated autoimmune disease gluten-sensitive enteropathy, leaving little room for a differential environmental trigger.
Previous evidence that non-MHCIDDM loci overlap RA susceptibility loci made IGFBP5 and its region an interesting candidate locus which was tested for linkage.
Lymphocytes from patients with insulin-dependent diabetes mellitus (IDDM), a chronic autoimmune disease, have recently been shown to have decreased surface expression of MHC class I antigens.
In the present study we characterized the frequencies of two polymorphisms within the MHC-linked heat shock protein (HSP) 70 genes in patients with insulin-dependent diabetes mellitus (IDDM) (n = 114) and healthy control individuals (n = 110).