title: GM-CSF/IL-3/IL-5 receptor common beta chain (CD131) expression as a biomarker of antigen-stimulated CD8+ T cells.
abstract: BACKGROUND
  Upon Ag-activation cytotoxic T cells (CTLs) produce IFN-gamma GM-CSF and TNF-alpha, which deliver simultaneously pro-apoptotic and pro-inflammatory signals to the surrounding microenvironment. Whether this secretion affects in an autocrine loop the CTLs themselves is unknown.
  
  
  METHODS
  Here, we compared the transcriptional profile of Ag-activated, Flu-specific CTL stimulated with the FLU M1:58-66 peptide to that of convivial CTLs expanded in vitro in the same culture. PBMCs from 6 HLA-A*0201 expressing donors were expanded for 7 days in culture following Flu M1:58-66 stimulation in the presence of 300 IU/ml of interleukin-2 and than sorted by high speed sorting to high purity CD8+ expressing T cells gated according to FluM1:58-66 tetrameric human leukocyte antigen complexes expression.
  
  
  RESULTS
  Ag-activated CTLs displayed higher levels of IFN-gamma, GM-CSF (CSF2) and GM-CSF/IL-3/IL-5 receptor common beta- chain (CD131) but lacked completely expression of IFN-gamma receptor-II and IFN-stimulated genes (ISGs). This observation suggested that Ag-activated CTLs in preparation for the release of IFN-gamma and GM-CSF shield themselves from the potentially apoptotic effects of the former entrusting their survival to GM-SCF. In vitro phenotyping confirmed the selective surface expression of CD131 by Ag-activated CTLs and their increased proliferation upon exogenous administration of GM-CSF.
  
  
  CONCLUSIONS
  The selective responsiveness of Ag-activated CTLs to GM-CSF may provide an alternative explanation to the usefulness of this chemokine as an adjuvant for T cell aimed vaccines. Moreover, the selective expression of CD131 by Ag-activated CTLs proposes CD131 as a novel biomarker of Ag-dependent CTL activation.
authors.affiliation: Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA. silvia.selleri@unimi.it
authors.forename: Silvia
authors.initials: S
authors.lastname: Selleri
authors.forename: Sara
authors.initials: S
authors.lastname: Deola
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Pos
authors.forename: Ping
authors.initials: P
authors.lastname: Jin
authors.forename: Andrea
authors.initials: A
authors.lastname: Worschech
authors.forename: Stefanie L
authors.initials: SL
authors.lastname: Slezak
authors.forename: Cristiano
authors.initials: C
authors.lastname: Rumio
authors.forename: Monica C
authors.initials: MC
authors.lastname: Panelli
authors.forename: Dragan
authors.initials: D
authors.lastname: Maric
authors.forename: David F
authors.initials: DF
authors.lastname: Stroncek
authors.forename: Ena
authors.initials: E
authors.lastname: Wang
authors.forename: Francesco M
authors.initials: FM
authors.lastname: Marincola
mesh_terms: D000956:Antigens, Viral / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D053648:Cytokine Receptor Common beta Subunit / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D009975:Orthomyxoviridae / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000378:metabolism
chemical_list: D000956:Antigens, Viral; D000970:Antineoplastic Agents; D015415:Biomarkers; D053648:Cytokine Receptor Common beta Subunit; D007376:Interleukin-2; D014763:Viral Matrix Proteins