Because T cell responses to tetanus toxoid or concanavalin A were not suppressed, it is unlikely that rosiglitazone has a toxic effect on the islet-reacting T cells but, rather, instills regulation of the autoimmune T cell response. Other markers of inflammation and autoimmunity were also down-regulated in the rosiglitazone-treated patients (IFN-γ and IL-12) compared to the glyburide-treated

patients. Additionally, the anti-inflammatory cytokine, C59 wnt adiponectin, was significantly (P < 0·001) higher at 12 months of follow-up in the plasma of the rosiglitazone-treated patients coinciding with down-regulation of the islet-specific T cell responses. In contrast, the adiponectin levels in the plasma of the glyburide-treated patients were not different from baseline during follow-up. In other autoimmune diseases, rosiglitazone has been

shown to be effective in reducing the development of inflammation and autoimmunity by increasing levels of regulatory cytokines such as IL-4 and IL-10, increasing CT99021 ic50 adiponectin, inhibiting T helper cell proliferative responses and decreasing IL-12 production [2, 40-45]. We hypothesized that the beneficial effects of thiazolidinediones (TZDs) in treating type 2 diabetes may be explained partly by the down-regulation of islet autoimmunity in these patients. Our data suggest that this may indeed be one mechanism of action of the TZDs in type 2 diabetes. We therefore propose that part of the clinical efficacy of rosiglitazone therapy on beta cell function in autoimmune T2DM patients results Phosphatidylinositol diacylglycerol-lyase from the immunosuppressive effects on the islet-specific autoreactive T cell responses and cytokine (IL-12 and IFN-γ) production and the up-regulation of adiponectin.

Thus, assessment of islet T cell autoimmunity may be important to determine whether phenotypic T2DM patients might benefit from treatment with rosiglitazone or other anti-inflammatory medications capable of suppressing islet-specific T cell autoimmunity. This work was supported (in part) by the Medical Research Service of the Department of Veterans Affairs and GlaxoSmithKline. In addition, the following National Institutes of Health grants provided partial support: P01-DK053004, P30-DK017047. We would also like to thank Mrs Jessica Reichow for help in preparation of this manuscript. This study was supported in part by an investigator-initiated grant from Glaxo-SmithKline. Dr Jerry Palmer has been a consultant for and been on the speakers’ bureau for Glaxo-SmithKline. “
“CD22 (Siglec-2) is a B-cell membrane-bound lectin that recognizes glycan ligands containing α2,6-linked sialic acid (α2,6Sia) and negatively regulates signaling through the B-cell Ag receptor (BCR).