Diabetes and other autoimmune endocrine diseases

Oral

Helios and cd127 Expression in cd8 Central Memory Cells Are Associated with Disease Progression in t1d

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

Residual C-peptide in Type 1 diabetes (T1D) indicates the persistence of beta cell function and insulin production and is a key therapeutic goal in the treatment of T1D. T cells are known to be involved in T1D pathogenesis. Thus, we designed a study to test T cell immune correlates of residual C-peptide using a cross-sectional cohort of T1D patients with varying levels of disease progression; slow progressors (n=33) maintained at least 0.1ng/mL of C-peptide, whereas rapid progressors (n=32) had C-peptide levels less than 0.1ng/mL within 5 years of diagnosis. We characterized PBMCs using multicolor flow cytometry and then compared T cell populations with clinical data. Compared to rapid progressors, slow progressors had significantly increased CD127 expression on CD8 central memory (CM) cells and decreased Helios expression on CD8 effector memory RA cells. As a continuous variable, higher C-peptide levels correlated with diminished total CD8 CM cells, and decreased Helios and CD28 expression within CD8 CM. Increased CD127 expression on CD8 CM cells was also observed in patients diagnosed at a later age. In an independent set of T1D samples analyzed by mass cytometry, islet-specific CD8 T cells were marked by increased CD127 expression compared to virus-reactive cells. Together, these observations suggest that CD127 and Helios on CD8 memory subsets may be an immune correlate of disease progression, and suggest involvement of a chronic activation phenotype in CD8 CM cells with more aggressive disease. Future studies will validate these findings and address the associations of this phenotype with genetic risk profile.

Megan DIANE. Maerz

Research Technician II
Benaroya Research Institute

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    Jerill Thorpe

    Benaroya Research Institute

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      Alice Wiedeman

      Benaroya Research Institute

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        Eddie James

        Assistant Member
        Benaroya Research Institute

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          Karen Cerosaletti

          Benaroya Research Institute

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            Cate Speake

            Benaroya Research Instutute

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              Carla Greenbaum

              Director, Diabetes Program
              Benaroya Research Institute

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                S. Alice Long

                Benaroya Research Institute

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