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Bender, C.* ; Rodriguez-Calvo, T. ; Amirian, N.* ; Coppieters, K.T.* ; Von Herrath, M.G.*

The healthy exocrine pancreas contains preproinsulin-specific CD8 T cells that attack islets in type 1 diabetes.

Sci. Adv. 6:eabc5586 (2020)

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Preproinsulin (PPI) is presumably a crucial islet autoantigen found in patients with type 1 diabetes (T1D) but is also recognized by CD8(+) T cells from healthy individuals. We quantified PPI-specific CD8(+) T cells within different areas of the human pancreas from nondiabetic controls, autoantibody-positive donors, and donors with T1D to investigate their role in diabetes development. This spatial cellular quantitation revealed unusually high frequencies of autoreactive CD8(+) T cells supporting the hypothesis that PPI is indeed a key autoantigen. To our surprise, PPI-specific CD8(+) T cells were already abundantly present in the nondiabetic pancreas, thus questioning the dogma that T1D is caused by defective thymic deletion or systemic immune dysregulation. During T1D development, these cells accumulated in and around islets, indicating that an islet-specific trigger such as up-regulation of major histocompatibility complex class I might be essential to unmask beta cells to the immune system.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Insulitic Lesions; Recent-onset; Beta-cells; Self; Pathogenesis; Proinsulin; Antigens; Develop; Ctls; Map

ISSN (print) / ISBN 2375-2548

e-ISSN 2375-2548

Journal Science Advances

Quellenangaben Volume: 6, Issue: 42, Article Number: eabc5586

Publisher American Association for the Advancement of Science (AAAS)

Publishing Place Washington, DC [u.a.]

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Diabetes Research Type 1 (IDF)

Grants German research funding organization (DFG)
National Institutes of Health (NIH)
nPOD, a collaborative type 1 diabetes research project - JDRF