Immunology of Type 1 Diabetes Mellitus

Type 1 diabetes mellitus (T1DM) is caused by autoimmune destruction of the insulin-secreting cells within the islets of Langerhans and Type 1 diabetic patients generally require exogenous insulin to survive. The autoimmune nature of this disease was elegantly demonstrated when a recipient affected by T1DM was transplanted with pancreatic tissue from a discordant monozygotic twin. In the absence of immunosuppression, the pancreatic β cells within the graft were destroyed by an autoimmune reaction. The fact that in both humans and animal models of autoimmune diabetes a number of immunosuppressive treatments can alter the disease course strengthens the latter observation. Pancreas or islet transplantation can reverse hyperglycemia, but unfortunately require lifelong immunosuppression and mechanisms controlling transplantation tolerance and autoimmunity may be potentially different. The association of certain human leukocyte antigen (HLA) alleles with T1DM is very strong, and this genetic locus is estimated to account for approximately 50% of genetic contributions to disease susceptibility. The search for non-HLA susceptibility genes has received great attention in recent years and genome wide scans yielded a stampede of data suggesting the association of numerous non-MHC loci with T1DM that still require careful follow-up examination.