GM-CSF/IL-3/IL-5 receptor common beta chain (CD131) expression as a biomarker of antigen-stimulated CD8+ T cells.
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.
Selleri
Silvia
S
Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA. silvia.selleri@unimi.it
Deola
Sara
S
Pos
Zoltan
Z
Jin
Ping
P
Worschech
Andrea
A
Slezak
Stefanie L
SL
Rumio
Cristiano
C
Panelli
Monica C
MC
Maric
Dragan
D
Stroncek
David F
DF
Wang
Ena
E
Marincola
Francesco M
FM
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
D000956:Antigens, Viral; D000970:Antineoplastic Agents; D015415:Biomarkers; D053648:Cytokine Receptor Common beta Subunit; D007376:Interleukin-2; D014763:Viral Matrix Proteins