The many faces of islet antigen‐specific CD8 T cells: clues to clinical outcome in type 1 diabetes

Immune monitoring enables a better understanding of disease processes and response to therapy, but has been challenging in the setting of chronic autoimmunity because of unknown etiology, variable and protracted kinetics of the disease process, heterogeneity across patients and the complexity of imm...

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Bibliographic Details
Published in:Immunology and cell biology 2021-05, Vol.99 (5), p.475-485
Main Authors: Wiedeman, Alice E, Speake, Cate, Long, Sarah Alice
Format: Article
Language:English
Subjects:
Antigens
antigen‐specific
Autoimmune diseases
Autoimmunity
CD8 antigen
CD8 T cells
Clinical outcomes
Diabetes
Diabetes mellitus (insulin dependent)
Etiology
exhaustion
Lymphocytes
Lymphocytes T
SPECIAL FEATURE to celebrate 100 years since the discovery of insulin
type 1 diabetes
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Summary:Immune monitoring enables a better understanding of disease processes and response to therapy, but has been challenging in the setting of chronic autoimmunity because of unknown etiology, variable and protracted kinetics of the disease process, heterogeneity across patients and the complexity of immune interactions. To begin to parse this complexity, we focus here on type 1 diabetes (T1D) and CD8 T cells as a cell type that has features that are associated with different stages of disease, rates of progression and response to therapy. Specifically, we discuss the current understanding of the role of autoreactive CD8 T cells in disease outcome, which implicates particular CD8 functional subsets, rather than unique antigens or total number of autoreactive T cells. Next, we discuss how autoreactive CD8 T‐cell features can be reflected in measures of global CD8 T cells, and then pull these concepts together by highlighting immune therapies recently shown to modulate both CD8 T cells and disease progression. We end by discussing outstanding questions about the role of specific subsets of autoreactive CD8 T cells in disease progression and how they may be optimally modulated to treat and prevent T1D. Studies implicate particular autoreactive CD8 T‐cell functional subsets, rather than certain self‐antigen specificities or the total number of cells, in type 1 diabetes (T1D) outcome. Specifically, more hyporesponsive and terminal subsets (i.e. exhausted cells) are associated with preservation of insulin‐producing beta islet cells while more progenitor, polyfunctional subsets are associated with poor outcome. A better understanding of the development of such CD8 T‐cell subsets in T1D will inform how they may be specifically and optimally modulated to treat and prevent T1D.
ISSN:0818-9641
1440-1711
DOI:10.1111/imcb.12437