Abstract
Type 1 diabetes (T1D) is a chronic autoimmune disease and characterized by absolute insulin deficiency. β-cell replacement by islet cell transplantation has been established as a feasible treatment option for T1D. The two main obstacles after islet transplantation are alloreactive T-cell-mediated graft rejection and recurrence of autoimmune diabetes mellitus in recipients. T cells play a central role in determining the outcome of both autoimmune responses and allograft survival. B7-H4, a newly identified B7 homolog, plays a key role in maintaining T-cell homeostasis by reducing T-cell proliferation and cytokine production. The relationship between B7-H4 and allograft survival/autoimmunity has been investigated recently in both islet transplantation and the nonobese diabetic (NOD) mouse models. B7-H4 protects allograft survival and generates donor-specific tolerance. It also prevents the development of autoimmune diabetes. More importantly, B7-H4 plays an indispensable role in alloimmunity in the absence of the classic CD28/CTLA-4 : B7 pathway, suggesting a synergistic/additive effect with other agents such as CTLA-4 on inhibition of unwanted immune responses.
Highlights
Type 1 diabetes (T1D) is fatal unless treated with insulin
Combination of intensive glycemic monitoring and best medical therapy provides better control of insulin level and reduces the microvascular and macrovascular complications of diabetes, but it increases the risk of severe hypoglycemia [1,2,3]
Recognition of foreign antigens presented on major histocompatibility complex (MHC) molecules by T-cell receptors (TCR) initiates T-cell-mediated immune responses that result in the destruction of transplanted grafts
Summary
Type 1 diabetes (T1D) is fatal unless treated with insulin. Injection of insulin prevents the hyperglycemic complications of T1D, including ketoacidosis and coma. The strategies for expanding donor islet supply include the construction of insulinproducing cells de novo. The current glucocorticoid-free immunosuppressive regimen for islet transplantation includes tacrolimus (FK506) and either sirolimus (rapamycin) or mycophenolate mofetil (MMF). These immunosuppressive drugs control acute rejection and enhance islet allograft survival, lack of long-term efficacy/insulin independence and immunosuppressant-associated side effects (including risks of cancer, infection, nephrotoxicity, cardiovascular-related diseases, and even direct islet toxicity) hamper this great application. All types of immunosuppressive drugs are presumed to have some degree of nonspecific toxicity In this regard, islet graft function should be better maintained in the absence of long-term ongoing immunosuppression. An ultimate goal in transplantation is to induce antigen-specific tolerance
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
