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

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.This article is protected by copyright. All rights reserved

Leveraging genetics to investigate causal effects of immune cell phenotypes in periodontitis: a mendelian randomization study

“…In another study, Gunderson et al found that CD8 + T cells induced psoriatic-like skin inflammation through IFN-γmediated pathways (Gunderson et al, 2013). Conversely, Wu et al observed that CD8 T cells could regulate autoreactive Th1 and Th17 cells via IFN-γ, thereby reducing neuroretinal inflammation in mice (Wu et al, 2023). Hence, we speculate that the role of CD8 in modulating the inflammatory response may be dual, with outcomes influenced by factors such as the disease site or type, animal model, or target population.…”

Efficacy of Corticosteroids in the Treatment of Autoimmune Uveitis and its Effect on T Helper Cell and S100 Protein Levels in Peripheral Blood

“…Th17 cells are implicated in the pathogenesis of various autoimmune diseases, and pathogenic Th17 cells are thought to induce immune cell infiltration and tissue damage by secreting pro-inflammatory cytokines, including IL-17A, IL-17F, IL-22, and granulocyte-macrophage colony-stimulating factor. Numerous studies using experimental autoimmune uveitis animal models have demonstrated that retinal antigen specific Th1 and Th17 cells can induce autoimmune uveitis in naive mice through adoptive transfer [5,8] . In this study, compared to the non-uveitis group, the proportions of Th1 and Th17 cells in uveitis patients were significantly elevated before treatment.…”

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“…In another study, Gunderson et al found that CD8 + T cells induced psoriatic-like skin inflammation through IFN-γmediated pathways (Gunderson et al, 2013). Conversely, Wu et al observed that CD8 T cells could regulate autoreactive Th1 and Th17 cells via IFN-γ, thereby reducing neuroretinal inflammation in mice (Wu et al, 2023). Hence, we speculate that the role of CD8 in modulating the inflammatory response may be dual, with outcomes influenced by factors such as the disease site or type, animal model, or target population.…”