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

Silvia Selleri¹^,2 , Sara Deola² , Zoltan Pos¹ , Ping Jin¹ , Andrea Worschech¹ , Stefanie L Slezak³ , Cristiano Rumio⁴ , Monica C Panelli⁵ , Dragan Maric⁶ , David F Stroncek³ , Ena Wang¹ and Francesco M Marincola¹

¹Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA

²Hematology and BMT Unit, Scientific Institute H S. Raffaele, Milan, Italy

³Cell Processing Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA

⁴Department of Human Morphology, Universitá degli Studi di Milano, Milan, Italy

⁵Department of Medicine, University of Pittsburgh Cancer Center, Pittsburg, PA, USA

⁶Laboratory of Kidney and Electrolyte Metabolism, NHLBI, NIH, Bethesda, MD, USA

author email corresponding author email

Journal of Translational Medicine 2008, 6:17doi:10.1186/1479-5876-6-17


Published:	15 April 2008

Abstract

Background

Upon Ag-activation cytotoxic T cells (CTLs) produce IFN-γ GM-CSF and TNF-α, 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-γ, GM-CSF (CSF2) and GM-CSF/IL-3/IL-5 receptor common β- chain (CD131) but lacked completely expression of IFN-γ receptor-II and IFN-stimulated genes (ISGs). This observation suggested that Ag-activated CTLs in preparation for the release of IFN-γ 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.