Autoantibodies and T cells reacting with islet proteins have been demonstrated in type 1 and type 1.5 diabetes patients. In contrast, classic autoantibody type 2 diabetes patients are negative for T cell responses to islet proteins. In this study, we investigated whether there is a subset of adult type 2 diabetes patients who are autoantibody (ICA/IAA/GAD/IA-2) negative but who have T cell responses to islet proteins. Furthermore, an immunoregulatory circuit (IL-10/IL-12) has been proposed to play a critical role in modulating development of autoimmunity. In this study, we investigated T cell proliferative responses to islet proteins using cellular immunoblotting and cytokine responses (IL-10 and IL-12) using ELISPOT to sonicated islets and soluble insulin. Amongst 15 autoantibody (ICA/IAA/GAD/IA-2) negative type 2 diabetes patients we identified six who demonstrated T cell proliferative responses to islet proteins and 9 patients who were negative for T cell proliferative responses to islet proteins. We then asked whether there was a difference in the IL-10/IL-12 ratio to islet proteins and insulin, using ELISPOT, and whether there was a difference in beta-cell function between patients who were T cell positive or T cell negative. Fasting and glucagon-stimulated C-peptide levels were used to assess beta-cell function. The IL-10/IL-12 ratio was higher in response to human sonicated islets and insulin in the T cell negative type 2 patients compared to the T cell positive patients, though not significant (p=0.09). Mean fasting c-peptide was not different between the two groups. However, the stimulated c-peptide was significantly (p≤0.05) lower in the patients with T cell responses to islet proteins compared to the patients negative for T cell responses. This data suggests that T cell proliferative and cytokine responses to islet proteins may identify amongst autoantibody negative type 2 diabetes patients, those patients with islet cell autoimmunity and more severe Beta-cell dysfunction. Thus, measurement of T cell responses to islet proteins in addition to detection of islet autoantibodies may aid in identifying patients with more severe Beta-cell dysfunction.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.