title: Th17 and non-Th17 interleukin-17-expressing cells in chronic lymphocytic leukemia: delineation, distribution, and clinical relevance.
abstract: BACKGROUND
  The levels and clinical relevance of Th17 cells and other interleukin-17-producing cells have not been analyzed in chronic lymphocytic leukemia. The objective of this study was to quantify blood and tissue levels of Th17 and other interleukin-17-producing cells in patients with this disease and correlate blood levels with clinical outcome.
  
  
  METHODS
  Intracellular interleukin-17A was assessed in blood and splenic mononuclear cells from patients with chronic lymphocytic leukemia and healthy subjects using flow cytometry. Interleukin-17A-producing cells were analyzed in formalin-fixed, paraffin-embedded spleen and lymph node sections using immunohistochemistry and immunofluorescence.
  
  
  RESULTS
  The absolute numbers of Th17 cells in peripheral blood mononuclear cells and the percentages of Th17 cells in spleen cell suspensions were higher in patients with chronic lymphocytic leukemia than in healthy subjects; in six out of eight paired chronic lymphocytic leukemia blood and spleen sample comparisons, Th17 cells were enriched in spleen suspensions. Circulating Th17 levels correlated with better prognostic markers and longer overall survival of the patients. Two "non-Th17" interleukin-17-expressing cells were identified in chronic lymphocytic leukemia spleens: proliferating cells of the granulocytic lineage and mature mast cells. Granulocytes and mast cells in normal spleens did not express interleukin-17. Conversely, both chronic lymphocytic leukemia and healthy lymph nodes contained similar numbers of interleukin-17+ mast cells as well as Th17 cells.
  
  
  CONCLUSIONS
  Th17 cells are elevated in chronic lymphocytic leukemia patients with better prognostic markers and correlate with longer survival. Furthermore, non-Th17 interleukin-17A-expressing cells exist in chronic lymphocytic leukemia spleens as maturing granulocytes and mature mast cells, suggesting that the microenvironmental milieu in leukemic spleens promotes the recruitment and/or expansion of Th17 and other IL-17-expressing cells. The pathophysiology of Th17 and non-Th17-interleukin-producing cells in chronic lymphocytic leukemia and their distributions and roles in this disease merit further study.
authors: The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY 11030, USA.
authors: Preetesh
authors: P
authors: Jain
authors: Mohammad
authors: M
authors: Javdan
authors: Franziska K
authors: FK
authors: Feger
authors: Pui Yan
authors: PY
authors: Chiu
authors: Cristina
authors: C
authors: Sison
authors: Rajendra N
authors: RN
authors: Damle
authors: Tawfiqul A
authors: TA
authors: Bhuiya
authors: Filiz
authors: F
authors: Sen
authors: Lynne V
authors: LV
authors: Abruzzo
authors: Jan A
authors: JA
authors: Burger
authors: Andreas
authors: A
authors: Rosenwald
authors: Steven L
authors: SL
authors: Allen
authors: Jonathan E
authors: JE
authors: Kolitz
authors: Kanti R
authors: KR
authors: Rai
authors: Nicholas
authors: N
authors: Chiorazzi
authors: Barbara
authors: B
authors: Sherry
mesh_terms: D006801:Humans; D016130:Immunophenotyping; D020381:Interleukin-17 / Q000378:metabolism*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000378:metabolism / Q000401:mortality; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D018655:Lymphocyte Count; D011379:Prognosis; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D016019:Survival Analysis; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D020381:Interleukin-17