title: Distinctive patterns of naïve/memory subset distribution and cytokine expression in CD4 T lymphocytes in ZAP-70 B-chronic lymphocytic patients.
abstract: BACKGROUND
  ZAP-70 upregulation in B chronic lymphocytic leukemia (B-CLL) cells is a recognized marker of poor prognosis in these patients; the biological basis of this differential clinical outcome nonetheless remains unknown. ZAP-70 overexpression is considered a surrogate marker of a B-CLL cell subset. To test whether the differential biological characteristics of these patients also include the T helper population, we studied naïve, non-terminated memory (NTEM), terminated memory (TEM) and central memory (CM) cells, and cytokine expression by CD4 T lymphocytes from ZAP-70(+) and ZAP-70(-) B-CLL patients.
  
  
  METHODS
  Expression of CD3, CD8, CD45RA, CD27, and CD28 antigens and intracytoplasmic cytokine production (IFNγ, IL-2, IL-4, IL-10, and TNFα) were assessed simultaneously by nine-color flow-cytometry in peripheral blood lymphocytes from B-CLL patients. B cell ZAP-70 expression in B-CLL cells was also analyzed by flow cytometry.
  
  
  RESULTS
  Compared to ZAP-70(-) B-CLL patients, ZAP-70(+) B-CLL patients showed 1) significant reduction in the naïve T helper subset and expansion of NTEM and TEM subsets, 2) a decrease in the percentage of activated CD4 T lymphocytes expressing IFNγ, TNFα, and IL-2, and 3) an increase in the percentage of CD4 T lymphocytes expressing IL-4 or IL-10.
  
  
  CONCLUSIONS
  In conclusion, in early stage B-CLL patients, ZAP-70 upregulation is associated with distinct patterns of activation/differentiation stage subset distribution and of cytokine expression in CD4 T lymphocytes.
authors.affiliation: Laboratory of Immune System Diseases and Oncology, Department of Medicine (CNB/CSIC Associated Unit), University of Alcalá, Alcala de Henares, 28871, Madrid, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Monserrat
authors.forename: Miguel Ángel
authors.initials: MÁ
authors.lastname: Sánchez
authors.forename: Raquel
authors.initials: R
authors.lastname: de Paz
authors.forename: David
authors.initials: D
authors.lastname: Díaz
authors.forename: Sonia
authors.initials: S
authors.lastname: Mur
authors.forename: Eduardo
authors.initials: E
authors.lastname: Reyes
authors.forename: Alfredo
authors.initials: A
authors.lastname: Prieto
authors.forename: Antonio
authors.initials: A
authors.lastname: de la Hera
authors.forename: Carlos
authors.initials: C
authors.lastname: Martínez-A
authors.forename: Melchor
authors.initials: M
authors.lastname: Alvarez-Mon
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D015854:Up-Regulation; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000096:biosynthesis* / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D016207:Cytokines; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human
keywords: B-CLL; CD4 T lymphocytes; ZAP-70; flow cytometry; intracellular cytokine production