The authors developed a novel assay to examine T cell responses to a panel of epitopes naturally expressed by islet cells and demonstrated that it is the pathways of T cell differentiation and maturation in reaction to these epitopes in T1DM patients (in whom autoimmunity develops) and normal individuals (in whom autoimmunity is arrested) that are different. Upon exposure to antigen, nave T cells in normal individuals differentiate into T cells that produce IL-10, and possibly TGF- beta, subsequently inhibiting cells that would normally mediate an aggressive immune response. The results reported by Peakman and colleagues suggest that in patients with T1DM, there is instead induction of a predominant number of T cells that produce IFN-gamma and IL-2, which drives an autoaggressive immune response. Why these T cell activation pathways differ between normal and T1DM patients will require further characterization.
In an accompanying commentary, Kevan Herald from the Naomi Berrie Diabetes Center at Columbia University,
Contact: Brooke Grindlinger
Journal of Clinical Investigation