title: T-Bet and Eomes Regulate the Balance between the Effector/Central Memory T Cells versus Memory Stem Like T Cells.
abstract: Memory T cells are composed of effector, central, and memory stem cells. Previous studies have implicated that both T-bet and Eomes are involved in the generation of effector and central memory CD8 T cells. The exact role of these transcription factors in shaping the memory T cell pool is not well understood, particularly with memory stem T cells. Here, we demonstrate that both T-bet or Eomes are required for elimination of established tumors by adoptively transferred CD8 T cells. We also examined the role of T-bet and Eomes in the generation of tumor-specific memory T cell subsets upon adoptive transfer. We showed that combined T-bet and Eomes deficiency resulted in a severe reduction in the number of effector/central memory T cells but an increase in the percentage of CD62L(high)CD44(low) Sca-1(+) T cells which were similar to the phenotype of memory stem T cells. Despite preserving large numbers of phenotypic memory stem T cells, the lack of both of T-bet and Eomes resulted in a profound defect in antitumor memory responses, suggesting T-bet and Eomes are crucial for the antitumor function of these memory T cells. Our study establishes that T-bet and Eomes cooperate to promote the phenotype of effector/central memory CD8 T cell versus that of memory stem like T cells.
authors.affiliation: Stem Cell Research Laboratory of Jiangsu Province, Jiangsu Institute of Clinical Immunology, Institute of Medical Biotechnology, Soochow University, Suzhou, Jiangsu, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.forename: Qianting
authors.initials: Q
authors.lastname: Yang
authors.forename: Yibei
authors.initials: Y
authors.lastname: Zhu
authors.forename: Hong-Rui
authors.initials: HR
authors.lastname: Wang
authors.forename: Xinchun
authors.initials: X
authors.lastname: Chen
authors.forename: Xueguang
authors.initials: X
authors.lastname: Zhang
authors.forename: Binfeng
authors.initials: B
authors.lastname: Lu
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000637:transplantation; D002478:Cells, Cultured; D007156:Immunologic Memory / Q000276:immunology*; D016219:Immunotherapy, Adoptive; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000473:pathology; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D013234:Stem Cells / Q000166:cytology / Q000276:immunology*; D020825:T-Box Domain Proteins / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D000098815:T-bet Transcription Factor
chemical_list: C491198:Eomes protein, mouse; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor