Autoimmune CD8+ T cells in type 1 diabetes: from single-cell RNA sequencing to T-cell receptor redirection

Front Endocrinol (Lausanne). 2024 May 10:15:1377322. doi: 10.3389/fendo.2024.1377322. eCollection 2024.

Abstract

Type 1 diabetes (T1D) is an organ-specific autoimmune disease caused by pancreatic β cell destruction and mediated primarily by autoreactive CD8+ T cells. It has been shown that only a small number of stem cell-like β cell-specific CD8+ T cells are needed to convert normal mice into T1D mice; thus, it is likely that T1D can be cured or significantly improved by modulating or altering self-reactive CD8+ T cells. However, stem cell-type, effector and exhausted CD8+ T cells play intricate and important roles in T1D. The highly diverse T-cell receptors (TCRs) also make precise and stable targeted therapy more difficult. Therefore, this review will investigate the mechanisms of autoimmune CD8+ T cells and TCRs in T1D, as well as the related single-cell RNA sequencing (ScRNA-Seq), CRISPR/Cas9, chimeric antigen receptor T-cell (CAR-T) and T-cell receptor-gene engineered T cells (TCR-T), for a detailed and clear overview. This review highlights that targeting CD8+ T cells and their TCRs may be a potential strategy for predicting or treating T1D.

Keywords: CD8+ T cells; CRISPR/Cas9; chimeric antigen receptor T-cell (CAR-T); single-cell RNA sequencing (scRNA-seq); type 1 diabetes.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoimmunity
  • CD8-Positive T-Lymphocytes* / immunology
  • Diabetes Mellitus, Type 1* / genetics
  • Diabetes Mellitus, Type 1* / immunology
  • Humans
  • Insulin-Secreting Cells / immunology
  • Insulin-Secreting Cells / metabolism
  • Mice
  • Receptors, Antigen, T-Cell* / genetics
  • Receptors, Antigen, T-Cell* / immunology
  • Receptors, Antigen, T-Cell* / metabolism
  • Sequence Analysis, RNA / methods
  • Single-Cell Analysis* / methods

Substances

  • Receptors, Antigen, T-Cell

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (Grant number 82260169) and the Science & Technology Department of JiangXi Province (Grant number 20224ACB216003).