Diabetes and other autoimmune endocrine diseases

Poster

Natural Killer Cell Frequency and Phenotype in Patients with Type 1 Diabetes

Thursday, June 15
5:45 PM - 7:00 PM

Multiple lines of evidence suggest viral infections may play a key role in the initiation of type 1 diabetes (T1D), including a type 1 interferon signature, MHC class I hyperexpression in pancreatic islets, and the presence of autoreactive CD8+ T cells thought to be directly cytotoxic to b-cells. However, there remains a paucity of data regarding the frequency, subsets, and activation state of natural killer (NK) cells in T1D. Here, we report on NK cells in a cross-sectional cohort of patients with established (> 3months duration) T1D (n=39; 25.7±16.1 y) first-degree relatives (n=26; 35.7±16.3 y) and healthy controls (n=36; 21.7±10.9 y). Whole peripheral blood was collected and analyzed by flow cytometry for the markers CD3, CD56, CD16, CD57, CD25, NKG2A, CD226 and TIGIT. In contrast to prior reports suggesting deficiencies, our results showed no significant differences when comparing patients to controls in the frequency of total NK cells or in the associated immature CD56bright and terminally differentiated CD57+ subsets. However, we did observe increased expression of the costimulatory receptor CD226 on NK cells in patients with T1D (P=0.0394), while expression of the negative regulatory TIGIT was comparable with that of controls. Moreover, we noted a decrease in the expression of the activation-dependent IL2RA (CD25), a T1D candidate gene, on NK cells in subjects with T1D (P=0.0084). Altogether, this study shows differences in NK cell receptor expression and activity in T1D, which may be useful for the development of biomarkers or rational therapies in the context of precision genomic medicine.

Joseph W. Dean

University of Florida

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    Daniel J. Perry

    Postdoctoral Associate
    University of Florida

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      Wen-I Yeh

      University of Florida

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        Maigan A. Brusko

        University of Florida

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          Howard R. Seay

          University of Florida

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            Todd M. Brusko

            University of Florida

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