Association of T-cell reactivity with β-cell function in recent onset type 1 diabetes patients

Abstract

Objective The aim of the current study was to investigate whether autoantigen directed T-cell reactivity relates to β-cell function during the first 78 weeks after diagnosis of type 1 diabetes. Research design and methods 50 adults and 49 children (mean age 27.3 and 10.9 years respectively) with recent onset type 1 diabetes who participated in a placebo-controlled trial of immune intervention with DiaPep277 were analyzed. Secretion of interferon (IFN)-γ, interleukin (IL)-5, IL-13 and IL-10 by single peripheral mononuclear cells (PBMC) upon stimulation with islet antigens GAD65, heat shock protein 60 (Hsp60) protein-tyrosine-phosphatase-like-antigen (pIA2) or tetanus toxoid (TT) was determined applying ELISPOT; β-cell function was evaluated by glucagon stimulated C-peptide. Multivariate regression analysis was applied. Results In general, number of islet antigen-reactive cells decreased over 78 weeks in both adults and children, whereas reactivity to TT was not reduced. In addition, there was an association between the quality of immune cell responses and β-cell function. Overall, increased responses by IFN-γ secreting cells were associated with lower β-cell function whereas IL-5, IL-13 and IL-10 cytokine responses were positively associated with β-cell function in adults and children. Essentially, the same results were obtained with three different models of regression analysis. Conclusions The number of detectable islet-reactive immune cells decreases within 1–2 years after diagnosis of type 1 diabetes. Cytokine production by antigen-specific PBMC reactivity is related to β-cell function as measured by stimulated C-peptide. Cellular immunity appears to regress soon after disease diagnosis and begin of insulin therapy.