title: T-cell receptor diversity is selectively skewed in T-cell populations of patients with Wiskott-Aldrich syndrome.
abstract: BACKGROUND
  Wiskott-Aldrich syndrome (WAS) is a severe disorder characterized by thrombocytopenia, eczema, immunodeficiency, and increased risk of autoimmune disease and lymphoid malignancies. The immunodeficiency caused by a lack of WAS protein expression has been mainly attributed to defective T-cell functions. Whether WAS mutations differentially influence the T-cell receptor (TCR) diversity of different T-cell subsets is unknown.
  
  
  OBJECTIVE
  We aimed to identify the degree and pattern of skewing in the variable region of the TCR β-chain (Vβ) in different T-cell subsets from patients with WAS.
  
  
  METHODS
  The TCR repertoire diversity in total peripheral T cells, sorted CD4(+) and CD8(+) T cells, and CD45RA(+) (CD45RA(+)CD45RO(-) cells) and CD45RO(+) (CD45RA(-)CD45RO(+) cells) CD4(+) and CD8(+) T cells from patients with WAS and age-matched healthy control subjects was analyzed and compared by using spectratyping of complementarity-determining region 3. The complementarity-determining region 3 of TCRβ transcripts in CD45RA(+)CD4(+) and CD45RA(+)CD8(+) T cells, CD45RO(+)CD4(+) T cells, CD8(+) terminally differentiated effector memory T (Temra) cells, and naive CD8(+) T cells (CD8(+)CD45RO(-)CCR7(+) cells) from patients and control subjects were analyzed and compared by using high-throughput sequencing.
  
  
  RESULTS
  The TCR repertoire diversity in CD45RO(+)CD4(+) T cells and CD8(+) Temra cells of patients with WAS was significantly skewed in comparison with that seen in age-matched control subjects.
  
  
  CONCLUSIONS
  Our results indicate that WAS gene mutations selectively influence TCR repertoire development or expansion in CD45RO(+) (memory) CD4(+) T cells.
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Wu
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, University of Hong Kong, Hong Kong, China.
authors.forename: Wenwei
authors.initials: W
authors.lastname: Tu
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Md.
authors.forename: Wenxia
authors.initials: W
authors.lastname: Song
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China. Electronic address: zhaoxd530@aliyun.com.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhao
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008297:Male; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014923:Wiskott-Aldrich Syndrome / Q000208:ethnology / Q000235:genetics / Q000276:immunology*; D051316:Wiskott-Aldrich Syndrome Protein / Q000235:genetics
chemical_list: D011948:Receptors, Antigen, T-Cell; C495767:WAS protein, human; D051316:Wiskott-Aldrich Syndrome Protein
keywords: T-cell receptor repertoire diversity; Wiskott-Aldrich syndrome; high-throughput sequencing