The Sentinel Role of CD8 T Cells in Regulating CD4 T Cell Responses to Proinsulin in β-Islet Cell Autoimmunity


Address for correspondence: Ivana Durinovic-Belló, Benaroya Research Institute at Virginia Mason, 1201 Ninth Avenue, Seattle, WA 98101-2795. Voice: +206-223-8813, ext. 6-7884; fax: +206-223-7638.


Circulating CD4 T cells specific for peptide epitopes of proinsulin and other autoantigens are markers of autoimmune β cell destruction in type 1 diabetes, while the role of CD8 T cells is still largely unknown. Here we show that CD8 T cells of a diabetic patient—after rechallange with proinsulin peptides—secrete IFNγ and granzyme B, markers of their effector capacity. On the other hand, CD8 T cells of the same patient in a “cross-talk” with proinsulin-specific CD4 T cells suppress their proliferation. If confirmed in larger numbers of subjects with β-islet cell autoimmunity, these results may help us to understand the role of CD8 cells in disease progression and extend our knowledge of disease pathogenesis.