Single-cell transcriptomics of human gut T cells identifies cytotoxic CD4+CD8A+ T cells related to mouse CD4 cytotoxic T cells

Shun Tanemoto, Tomohisa Sujino, Kentaro Miyamoto, Jonathan Moody, Yusuke Yoshimatsu, Yoshinari Ando, Ikuko Koya, Yosuke Harada, Anna Okuzawa Tojo, Keiko Ono, Yukie Hayashi, Kaoru Takabayashi, Koji Okabayashi, Toshiaki Teratani, Yohei Mikami, Nobuhiro Nakamoto, Naoki Hosoe, Haruhiko Ogata, Chung Chau Hon, Jay W. ShinTakanori Kanai

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


Cytotoxic CD4+ T cells (CD4-CTLs) show the presence of cytolytic granules, which include the enzymes granzyme and perforin. The cells have a pathogenic and protective role in various diseases, including cancer, viral infection, and autoimmune disease. In mice, cytotoxic CD4+ T cells express CD8αα+ and reside in the intestine (mouse CD4+CTLs; mCD4-CTLs). The population of cytotoxic CD4+ T cells in the human intestine is currently unknown. Moreover, it is unclear how cytotoxic CD4 T cells change in patients with inflammatory bowel disease (IBD). Here, we aimed to identify cytotoxic CD4+ T cells in the human intestine and analyze the characteristics of the population in patients with IBD using single-cell RNA-seq (scRNA-seq). In CD4+ T cells, granzyme and perforin expression was high in humanMAIT (hMAIT) cells and hCD4+CD8A+ T cell cluster. Both CD4 and CD8A were expressed in hTreg, hMAIT, and hCD4+CD8A+ T cell clusters. Next we performed fast gene set enrichment analysis to identify cell populations that showed homology to mCD4CTLs. The analysis identified the hCD4+CD8A+ T cell cluster (hCTL-like population; hCD4-CTL) similar to mouse CTLs. The percentage of CD4+CD8A+ T cells among the total CD4+ T cells in the inflamed intestine of the patients with Crohn’s disease was significantly reduced compared with that in the noninflamed intestine of the patients. In summary, we identified cytotoxic CD4+CD8+ T cells in the small intestine of humans. The integration of the mouse and human sc-RNA-seq data analysis highlight an approach to identify human cell populations related to mouse cell populations, which may help determine the functional properties of several human cell populations in mice.

Original languageEnglish
Article number977117
JournalFrontiers in Immunology
Publication statusPublished - 2022 Oct 24


  • cytotoxic CD4 T cells
  • human CD4CD8A T cells
  • inflammatory bowel disease
  • intestinal inflammation
  • single-cell RNA sequencing

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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