PLG scaffold delivered antigen-specific regulatory T cells induce systemic tolerance in autoimmune diabetes.

Islet transplantation is a promising treatment for human type 1 diabetes mellitus. Transplantation requires systemic immunosuppression, which has numerous deleterious side effects. Islet antigen-specific regulatory T cells (Tregs) have been shown to protect islet grafts from autoimmune destruction in the nonobese diabetic (NOD) model when co-localized in the kidney capsule.

Ethylenecarbodiimide-fixed donor splenocyte infusions differentially target direct and indirect pathways of allorecognition for induction of transplant tolerance.

Strategic exposure to donor Ags prior to transplantation can be an effective way for inducting donor-specific tolerance in allogeneic recipients. We have recently shown that pretransplant infusion of donor splenocytes treated with the chemical cross-linker ethylenecarbodiimide (ECDI-SPs) induces indefinite islet allograft survival in a full MHC-mismatched model without the need for any immunosuppression. Mechanisms of allograft protection by this strategy remain elusive.

Common gamma chain cytokines promote rapid in vitro expansion of allo-specific human CD8+ suppressor T cells.

Human CD8(+) regulatory T cells, particularly the CD8(+)CD28(-) T suppressor cells, have emerged as an important modulator of alloimmunity. Understanding the conditions under which these cells are induced and/or expanded would greatly facilitate their application in future clinical trials. In the current study, we develop a novel strategy that combines common gamma chain (γc) cytokines IL-2, IL-7 and IL-15 and donor antigen presenting cells (APCs) to stimulate full HLA-mismatched allogeneic human CD8(+) T cells which results in significant expansions of donor-specific CD8(+)CD28(-) T suppressor cells in vitro.

HSP90alpha and HSP90beta isoforms selectively modulate MHC class II antigen presentation in B cells.

Two isoforms of heat shock protein (HSP) 90, alpha and beta, are abundantly expressed in the cytoplasm of cells, yet only HSP90alpha serves as a chaperone to potentiate epitope presentation in the context of MHC class I molecules. By contrast, the role of HSP90 isoforms in MHC class II presentation of exogenous and endogenous Ags remains less clear. Studies here using human B lymphoblasts demonstrate the importance of HSP90alpha and HSP90beta isoforms in selectively regulating class II presentation of the diabetes autoantigen glutamic acid decarboxylase (GAD).

Type B insulin resistance developing during interferon-alpha therapy.

Objective: To report a rare case of diabetes caused by type B insulin resistance due to development of insulin receptor autoantibodies during treatment of hepatitis C with interferon-alpha and ribavirin.

Methods: Clinical and laboratory findings in the case are presented. The literature on type B insulin resistance and interferon-induced autoimmunity is reviewed.