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

Takeshi Kawabe, Thomas Ciucci, Kwang Soon Kim, Shunichi Tayama, Akihisa Kawajiri, Takumi Suzuki, Riou Tanaka, Naoto Ishii, Dragana Jankovic, Jinfang Zhu, Jonathan Sprent, Rémy Bosselut, Alan Sher

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


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.

Original languageEnglish
Article number870542
JournalFrontiers in immunology
Publication statusPublished - 2022 May 30
Externally publishedYes


  • CD4 T lymphocytes
  • homeostasis
  • innate immunity
  • memory
  • phenotypic analysis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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