title: The inducible T-cell co-stimulator molecule is expressed on subsets of T cells and is a new marker of lymphomas of T follicular helper cell-derivation.
abstract: BACKGROUND
  T follicular helper (T(FH)) cells reside in the light zone of germinal centers and are considered the cell of origin of angioimmunoblastic T-cell lymphoma. Recently, CXCL13, PD-1 and SAP were described as useful markers for T(FH) cells and angioimmunoblastic T-cell lymphoma but also reported in some peripheral T-cell lymphomas, not otherwise specified.
  
  
  METHODS
  In the present study the expression pattern of ICOS protein was investigated by immunohistochemistry-based techniques in routine sections of normal lymphoid tissues and 633 human lymphomas.
  
  
  RESULTS
  Cells strongly positive for ICOS were restricted to the light zone of germinal centers and co-expressed T(FH)-associated molecules. In addition, weak to moderate ICOS expression was observed in a small proportion of FOXP3-positive cells. In lymphomas, ICOS expression was confined to angioimmunoblastic T-cell lymphoma (85/86), peripheral T-cell lymphomas of follicular variant (18/18) and a proportion of peripheral T-cell lymphomas, not otherwise specified (24/56) that also expressed other T(FH)-associated molecules.
  
  
  CONCLUSIONS
  ICOS is a useful molecule for identifying T(FH) cells and its restricted expression to angioimmunoblastic T-cell lymphoma and a proportion of peripheral T-cell lymphomas, not otherwise specified (showing a T(FH)-like profile) suggests its inclusion in the antibody panel for diagnosing T(FH)-derived lymphomas. Our findings provide further evidence that the histological spectrum of T(FH)-derived lymphomas is broader than previously assumed.
authors.affiliation: Leukaemia Research Immunodiagnostics Unit, Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, Oxford, OX3 9DU, UK. teresa@marafioti.org.uk
authors.forename: Teresa
authors.initials: T
authors.lastname: Marafioti
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Paterson
authors.forename: Erica
authors.initials: E
authors.lastname: Ballabio
authors.forename: Andreas
authors.initials: A
authors.lastname: Chott
authors.forename: Yasodha
authors.initials: Y
authors.lastname: Natkunam
authors.forename: Manuel
authors.initials: M
authors.lastname: Rodriguez-Justo
authors.forename: Anne
authors.initials: A
authors.lastname: Plonquet
authors.forename: Socorro M
authors.initials: SM
authors.lastname: Rodriguez-Pinilla
authors.forename: Wolfram
authors.initials: W
authors.lastname: Klapper
authors.forename: Martin-L
authors.initials: ML
authors.lastname: Hansmann
authors.forename: Stefano A
authors.initials: SA
authors.lastname: Pileri
authors.forename: Peter G
authors.initials: PG
authors.lastname: Isaacson
authors.forename: Harald
authors.initials: H
authors.lastname: Stein
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Piris
authors.forename: David Y
authors.initials: DY
authors.lastname: Mason
authors.forename: Philippe
authors.initials: P
authors.lastname: Gaulard
mesh_terms: D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D007119:Immunoblastic Lymphadenopathy / Q000175:diagnosis* / Q000378:metabolism; D016130:Immunophenotyping; D060889:Inducible T-Cell Co-Stimulator Protein; D008224:Lymphoma, Follicular / Q000175:diagnosis* / Q000378:metabolism; D016411:Lymphoma, T-Cell, Peripheral / Q000175:diagnosis* / Q000378:metabolism; D011379:Prognosis; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism*
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D014408:Biomarkers, Tumor; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein