To Identify IKZF2~+ CD8~+ T Cells In Human Tissues And Explore Their Immune Function

Background:Regulatory T cells inhibit effector cells response,which is an important regulatory node in immune regulation to maintain immune homeostasis and immune tolerance and prevent autoimmunity.In addition to classical CD4~+Tregs,some subsets of CD8~+T cells also play inhibitory functions as Tregs.Recently,a subset of mouse CD8~+Ly49~+T cells expressing transcription factor IKZF2 have been found to play immunomodulator functions in various disease models and have a strong inhibitory effect on autoimmune responses.However,the evidence for IKZF2~+CD8~+T cells in humans is still insufficient.Objective:To explore the distribution and function of IKZF2~+CD8~+T cells in human body.Methods:IKZF2~+CD8~+T cells were separated by flow cytometry from peripheral blood,tonsils,lymph nodes,tumors and metastatic lymph nodes in human.Single cell RNA sequencing was performed to identify IKZF2~+CD8~+T cell subset and analyze their functions after obtaining single cell suspension of CD8~+T cells from tonsil samples of OSA patients.The distribution and function of IKZF2~+CD8~+T cells in tumor tissues were analyzed using open data.Single cell sequencing results of tonsil samples were compared between OSA patients with different degrees of hypoxia.The number and function of IKZF2~+CD8~+T cells in hypoxic state were analyzed.Results:Flow cytometry analysis of multiple tissues revealed the presence of a subset of CD8~+T cells expressing IKZF2 in humans.Single cell sequencing analysis identified IKZF2~+CD8~+T cell subsets in human tonsils.And gene function analysis showed that they had negative immunoregulatory effects.The distribution and function of IKZF2~+CD8~+T cells in tumor tissues are similar to that in tonsil tissues.The number and function of IKZF2~+CD8~+T cell subsets were down-regulated in tonsils of OSA patients with more hypoxia.Conclusions:IKZF2~+CD8~+T cell subsets exist in human body and play immunoregulatory functions.Hypoxia may be a mechanism that cause the changes in the number and function of these cells.