CD8+ T cells reduce neuroretina inflammation in mouse by regulating autoreactive Th1 and Th17 cells through IFN-γ

Sihan Wu, Xuan Zhang, Cuiping Hu, Yajie Zhong, Jun Chen*, Wai Po Chong*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

Abstract

Various regulatory CD8+ T-cell subsets have been proposed for immune tolerance and have been implicated in controlling autoimmune diseases. However, their phenotypic identities and suppression mechanisms are not yet understood. This study found that coculture of T-cell receptor (TCR)- or interferon (IFN)-β-activated CD8+ T cells significantly suppressed the cytokine production of Th1 and Th17 cells. By experimenting with the experimental autoimmune uveitis (EAU), we found that adoptive transfer of TCR or IFN-β-activated CD8 + T cells significantly lessened disease development in an IFN-γ-dependent manner with a decreased uveitogenic Th1 and Th17 response. Interestingly, after adoptive transfer into the EAU mice, the IFN-γ+CD8+ T cells were recruited more efficiently into the secondary lymphoid organs during the disease-priming phase. This recruitment depends on the IFN-γ-inducible chemokine receptor CXCR3; knocking out CXCR3 abolishes the protective effect of CD8+ T cells in EAU. In conclusion, we identified the critical role of IFN-γ for CD8+ T cells to inhibit Th1 and Th17 responses and ameliorate EAU. CXCR3 is necessary to recruit IFN-γ+CD8+ T cells to the secondary lymphoid organ for the regulation of autoreactive Th1 and Th17 cells.

Original languageEnglish
Article number2350574
Number of pages13
JournalEuropean Journal of Immunology
Volume53
Issue number12
Early online date9 Sept 2023
DOIs
Publication statusPublished - Dec 2023

Scopus Subject Areas

  • Immunology and Allergy
  • Immunology

User-Defined Keywords

  • Autoimmunity
  • CD8+ T cells
  • CXCR3
  • IFNs
  • Uveitis

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