Beta Cell-specific CD8 T Cells Maintain Stem Cell Memory-associated Epigenetic Programs During Type 1 Diabetes

Overview

Journal Nat Immunol

Date 2020 Apr 2

PMID 32231298

Citations 58

Authors

Hossam A Abdelsamed

Caitlin C Zebley

Hai Nguyen

Rachel L Rutishauser

Yiping Fan

Hazem E Ghoneim

Jeremy Chase Crawford

Francesca Alfei

Shanta Alli

Susan Pereira Ribeiro

Ashley H Castellaw

Maureen A McGargill

Hongjian Jin

Shannon K Boi

Cate Speake

Elisavet Serti

Laurence A Turka

Michael E Busch

Mars Stone

Steven G Deeks

Rafick-Pierre Sekaly

Dietmar Zehn

Eddie A James

Gerald T Nepom

Ben Youngblood

Affiliations

Soon will be listed here.

Abstract

The pool of beta cell-specific CD8 T cells in type 1 diabetes (T1D) sustains an autoreactive potential despite having access to a constant source of antigen. To investigate the long-lived nature of these cells, we established a DNA methylation-based T cell 'multipotency index' and found that beta cell-specific CD8 T cells retained a stem-like epigenetic multipotency score. Single-cell assay for transposase-accessible chromatin using sequencing confirmed the coexistence of naive and effector-associated epigenetic programs in individual beta cell-specific CD8 T cells. Assessment of beta cell-specific CD8 T cell anatomical distribution and the establishment of stem-associated epigenetic programs revealed that self-reactive CD8 T cells isolated from murine lymphoid tissue retained developmentally plastic phenotypic and epigenetic profiles relative to the same cells isolated from the pancreas. Collectively, these data provide new insight into the longevity of beta cell-specific CD8 T cell responses and document the use of this methylation-based multipotency index for investigating human and mouse CD8 T cell differentiation.

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