Science｜Li Jing et al. discovered and identified CD8+ T cell subsets with regulatory functions in the human body

The incidence of autoimmune diseases in the global population is about 7.
6% to 9.
4%, and it is showing a rising trend.
However, the pathogenesis and regulatory mechanism of most autoimmune diseases are not yet clear, so there is a lack of targeted treatment methods
.

Studies have found that CD8+ T cells expressing Ly49 receptors in mice have immunomodulatory functions [1], and can specifically kill MOG-specific pathogenic CD4 cells in a mouse model of experimental autoimmune encephalomyelitis (EAE).
+ T cells [2], thereby inhibiting disease progression
.

However, it is unclear whether similar CD8+ T cells exist in humans and whether they play a broader role in maintaining immune tolerance
.

Answering these questions is crucial for further understanding the occurrence and regulation of human autoimmune diseases and identifying new targets for the treatment of autoimmune diseases
.

On March 8, 2022, the Stanford University research team published a research paper titled KIR+CD8+ T cells suppress pathogenic T cells and are active in autoimmune diseases and COVID-19 in the journal Science, discovering and identifying regulatory functions in the human body of CD8+ T cell subsets
.

Among them, Professor Mark Davis (Academician of the National Academy of Sciences, Academician of the Academy of Arts and Sciences, HHMI researcher) and Professor Naresha Saligrama are the co-corresponding authors, and postdoctoral fellow Li Jing is the first author
.

Although humans do not express Ly49 homologous proteins, killer cell immunoglobulin-like receptors (KIRs), like Ly49 family proteins, have co-evolved with their ligands, the major histocompatibility complex I (MHC I), and KIRs are therefore considered to be It is the corresponding protein of mouse Ly49 in humans
.

The authors found that the proportion of KIR+CD8+ T cells in the peripheral blood and affected organs of patients with autoimmune diseases increased, and that KIR+CD8+ T cells could recognize and kill celiac disease patients through T cell receptor (TCR)/MHC I Gliadin-specific pathogenic CD4+ T cells in peripheral blood
.

In addition, transcriptome analysis showed that the gene expression of KIR+CD8+ T cells was highly similar to that of mouse Ly49+CD8+ T cells
.

Therefore, KIR+CD8+ T cells in humans have similar functions and phenotypes as Ly49+CD8+ T cells in mice
.

Since pathogen infection may break through immune tolerance and activate self-antigen-specific T cells to trigger an autoimmune response, the authors also analyzed the levels of KIR+CD8+ T cells in human infectious diseases
.

The proportion of KIR+CD8+T cells in the peripheral blood of patients with COVID-19 and influenza is significantly higher than that of healthy people, and is positively correlated with the occurrence of complications of COVID-19 vasculitis, and vasculitis may be induced by autoimmune reactions, so KIR The elevation of +CD8+ T cells may be related to the autoimmune response induced by SARS-CoV-2 infection
.

In order to further elucidate the function of such CD8+ T cells in infectious diseases, the authors used gene editing to specifically remove Ly49+ CD8+ T cells in mice and established mouse LCMV and influenza virus infection models, and found that Ly49+CD8+ +T cells are not involved in the regulation of antiviral immune responses, but can suppress autoimmune responses triggered by pathogen infection
.

In conclusion, the authors discovered and identified a new subset of CD8+ T cells with regulatory functions in humans, which can selectively suppress pathogenic T cells that trigger autoimmune responses, thereby contributing to the maintenance of peripheral immune tolerance.
play an important role in
.

Their mechanism of maintaining immune tolerance is different from that of traditional CD4+ regulatory T cells (Treg) and may complement the role of CD4+ Treg
.

These findings have important implications for understanding the link between autoimmune disease and pathogen infection, understanding key mechanisms leading to immune dysregulation, and developing future therapeutics targeting KIR+CD8+ T cells
.

Original link: https:// Publisher: Eleven References 1.
HJ Kim et al.
, CD8+ T regulatory cells express the Ly49 Class I MHC receptor and are defective in autoimmune prone B6-Yaa mice.
Proc Natl Acad Sci USA 108, 2010-2015 (2011).
2.
N.
Saligrama et al.
, Opposing T cell responses in experimental autoimmune encephalomyelitis.
Nature 572, 481-487 (2019).
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