GM-CSF/IL-3/IL-5 receptor common beta chain (CD131) expression as a biomarker of antigen-stimulated CD8+ T cells

J Transl Med. 2008 Apr 15:6:17. doi: 10.1186/1479-5876-6-17.

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.

Conclusion: 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.

MeSH terms

  • Antigens, Viral / metabolism*
  • Antineoplastic Agents / pharmacology
  • Biomarkers / metabolism
  • Cells, Cultured
  • Cytokine Receptor Common beta Subunit / genetics
  • Cytokine Receptor Common beta Subunit / metabolism*
  • Gene Expression Profiling
  • Humans
  • Interleukin-2 / pharmacology
  • Lymphocyte Activation*
  • Orthomyxoviridae / immunology*
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / immunology*
  • Up-Regulation / immunology*
  • Viral Matrix Proteins / metabolism

Substances

  • Antigens, Viral
  • Antineoplastic Agents
  • Biomarkers
  • Cytokine Receptor Common beta Subunit
  • Interleukin-2
  • Viral Matrix Proteins