title: CD117+CD44+Stem T Cells Develop in the Thymus and Potently Suppress T-cell Proliferation by Modulating the CTLA-4 Pathway.
abstract: CD117 is expressed on double-negative (DN; CD4-CD8-) cells (Nat Rev Immunol 14:529-545; 2014), but whether it is expressed in other stages and its subsequent functions are unclear. We used an improved method of flow cytometry to analyze different populations of thymocytes (Sci Rep 4:5781; 2014). The expression of CD117 and CTLA-4 were directly assayed in the early stage of thymocytes.
  
  
  
  Flow cytometry was used to analyze different populations of thymocytes, and T-cell proliferation assays, RT-PCR, and real-time RT-PCR were used to characterize the stem cells and examine the function of CD44+CD117+cells.
  
  
  
  In DN cells, CD117 expression was greatest on CD44+CD25+cells (DN2), followed by CD44+CD25-(DN1), CD44-CD25+(DN3), and CD44-CD25-(DN4) cells. In thymocytes, CD117 expression was highest in DN cells, followed by single-positive (SP; CD4 or CD8) and double-positive (DP; CD4+CD8+) cells.  Especially, CD117 expression was positively associated with CD44 and CTLA-4 expression. CTLA-4 expression was highest in DN cells, followed by SP and DP cells. CTLA-4 expression was positively associated with CD25, CD44, and Foxp3 expression. CD44+CD117+T cells expressed more CTLA-4, which suppressed T-cell proliferation and blocked CTLA-4 to cause antibody-induced T-cell proliferation.
  
  
  
  These results suggest that CD44+CD117+T cells are stem cells and a specific T-cell phenotype that initially develops in the thymus, but they do not progress through DN3and DN4stages, lack a DP stage, and potently suppress T-cell proliferation and modulate the CTLA-4 pathway.
authors.affiliation: Immunology and Tumor Research Instituted, the First Affiliate Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, People's Republic of China.|Core Research Laboratory, the Second Affiliated Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710049, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Immunology and Tumor Research Instituted, the First Affiliate Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, People's Republic of China.|The First Affiliated Hospital, Jinzhou Medical University, Liaoning, 121004, People's Republic of China.
authors.forename: Zhansheng
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Immunology and Tumor Research Instituted, the First Affiliate Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, People's Republic of China.
authors.forename: Wen
authors.initials: W
authors.lastname: Gu
authors.affiliation: Clinical Research Center, Guangdong Medical Collage, Zhanjiang, Guangdong, 524001, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.affiliation: Immunology and Tumor Research Instituted, the First Affiliate Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, People's Republic of China.
authors.forename: Bingyin
authors.initials: B
authors.lastname: Shi
authors.affiliation: The School of Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, China.
authors.forename: Enqi
authors.initials: E
authors.lastname: Liu
authors.affiliation: Immunology and Tumor Research Instituted, the First Affiliate Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, People's Republic of China. xiantieliu@mail.xjtu.edu.cn.
authors.forename: Tie
authors.initials: T
authors.lastname: Liu
mesh_terms: D000818:Animals; D060908:CTLA-4 Antigen / Q000235:genetics / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D005434:Flow Cytometry; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018960:Hyaluronan Receptors; D019009:Proto-Oncogene Proteins c-kit
keywords: CD117; CD25; CD44; CTLA-4; Flow cytometry; Stem cell