Endothelial progenitor cells possess monocyte-like antigen-presenting and T-cell-co-stimulatory capacity.
BACKGROUND
Endothelial progenitor cells (EPC) home to sites of vascular repair and therefore have potential implications in allogenic transplantation settings and in various vascular diseases. This study was performed to investigate the antigen-presenting capacity of peripheral blood mononuclear cells-derived EPC and their T-cell co-stimulatory capacity compared with human vascular endothelial cells (HUVEC) or monocytes.


METHODS
EPC were isolated from peripheral blood mononuclear cells by adhesion to fibronectin. Antigen presentation and co-culture assays of EPC, HUVEC, monocytes, and dendritic cells with allogenic CD4 T cells were quantified by thymidine incorporation (cpm) and by quantitative reverse-transcriptase polymerase chain reaction (LightCycler) for cytokine production.


RESULTS
Flow cytometric analyses revealed an expression of endothelial antigens (e.g., KDR) as well as monocytic antigens (e.g., CD14) in EPC. EPC effectively presented Mycobacterium tuberculosis antigen MTB 85B to DB3 hybridoma, a cell line specifically recognizing MTB 85B presented by means of human leukocyte antigen-DR3. In phytohemaglutinin-based CD4 T-cell co-stimulation assays, EPC-induced proliferation and cytokine production was comparable with monocytes and dendritic cells, whereas HUVEC-induced T-cell co-stimulation was markedly weaker. In contrast to HUVEC, EPC as well as monocytes activated naïve CD4/CD45RA T cells. Blocking experiments using CTLA-4-IgG fusion protein identified the CD28/CD80/86 system as a major co-stimulatory pathway for EPC-dependent T-cell activation.


CONCLUSIONS
Although EPC exhibit endothelial-like surface markers, functional characteristics place these cells in a monocytic lineage. EPC also display antigen-presenting capacity similar to monocytes and much stronger than human vascular EC. Significant T-cell-activating potential will have to be expected from EPC when potentially used therapeutically, especially in allogenic transplant settings.
Raemer
Patrick C
PC
Department of Cardiology, University Hospital, University of Heidelberg, Germany.
Haemmerling
Susanne
S
Giese
Thomas
T
Canaday
David H
DH
Katus
Hugo A
HA
Dengler
Thomas J
TJ
Sivanandam
Vijayshankar G
VG
Shankar
Sivanandam G Vijay
SG
D000818:Animals; D000918:Antibody Specificity; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018929:Cell Culture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D042783:Endothelial Cells / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D009000:Monocytes / Q000276:immunology*; D013234:Stem Cells / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014471:Umbilical Veins
D000941:Antigens