Redefining the Foreign Antigen and Self-Driven Memory CD4+ T-Cell Compartments via Transcriptomic, Phenotypic, and Functional Analyses

Frontiers in Immunology

Thomas Ciucci¹  Kwang Soon Kim²  Takumi Suzuki³  Shunichi Tayama³  Riou Tanaka³  Naoto Ishii³  Akihisa Kawajiri³  Takeshi Kawabe⁴  Alan Sher⁴  Dragana Jankovic⁴  Rémy Bosselut⁶  Jinfang Zhu⁷  Jonathan Sprent⁸ 

[1] David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester, Rochester, NY, United States;Department of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, South Korea;Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Japan;Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States;Immunology Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia;Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States;Molecular and Cellular Immunoregulation Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States;St. Vincent’s Clinical School, University of New South Wales, Sydney, NSW, Australia;

关键词: CD4+ T lymphocytes;    memory;    homeostasis;    innate immunity;    phenotypic analysis;   

DOI  :  10.3389/fimmu.2022.870542

来源: DOAJ

【 摘 要 】

Under steady-state conditions, conventional CD4+ T lymphocytes are classically divided into naïve (CD44lo CD62Lhi) and memory (CD44hi CD62Llo) cell compartments. While the latter population is presumed to comprise a mixture of distinct subpopulations of explicit foreign antigen (Ag)-specific “authentic” memory and foreign Ag-independent memory-phenotype (MP) cells, phenotypic markers differentially expressed in these two cell types have yet to be identified. Moreover, while MP cells themselves have been previously described as heterogeneous, it is unknown whether they consist of distinct subsets defined by marker expression. In this study, we demonstrate using combined single-cell RNA sequencing and flow cytometric approaches that self-driven MP CD4+ T lymphocytes are divided into CD127hi Sca1lo, CD127hi Sca1hi, CD127lo Sca1hi, and CD127lo Sca1lo subpopulations that are Bcl2lo, while foreign Ag-specific memory cells are CD127hi Sca1hi Bcl2hi. We further show that among the four MP subsets, CD127hi Sca1hi lymphocytes represent the most mature and cell division-experienced subpopulation derived from peripheral naïve precursors. Finally, we provide evidence arguing that this MP subpopulation exerts the highest responsiveness to Th1-differentiating cytokines and can induce colitis. Together, our findings define MP CD4+ T lymphocytes as a unique, self-driven population consisting of distinct subsets that differ from conventional foreign Ag-specific memory cells in marker expression and establish functional relevance for the mature subset of CD127hi Sca1hi MP cells.

【 授权许可】

Unknown