Abstracts (complete list) - Wissenschaft Online

Patrick C. Rämer, Susanne Haemmerling, Mathias H. Konstandin, Thomas Giese,
Thomas J. Dengler, Sivanandam Vijayshankar
Antigen-presenting capacity and T cell costimulation of
endothelial progenitor cells is comparable to monocytes
Endothelial progenitor cells (EPC) home to sites of vascular repair and therefore have
potential implications in vascular diseases and in allogenic transplant settings. This
study aimed to investigate the antigen presenting capacity of EPC and their T cell
costimulatory capacity compared to HUVEC and monocytes.
EPCs were isolated from PBMCs by adhesion to fibronectin. Coculture assays of EPC,
HUVEC and monocytes were performed with allogenic CD4 T cells and were quantified
by thymidine incorporation. Cytokine production was assessed by qRT-PCR (Light
Cycler).
Flow-cytometric analyses revealed an expression of endothelial antigens (e.g. KDR) as
well as monocytic antigens (e.g. CD14). In PHA-based CD4 costimulation assays, EPC
induced similar stimulation indices (35) compared to monocytes (30), while HUVECinduced
proliferation was clearly less (~20). This T cell activation was strongly
dependent on B7-CD28 interaction, as blocking with CTLA-4 fusionprotein resulted in
70% decrease of proliferation. In addition, costimulation with EPC resulted in 6-fold
upregulation of IL-2 mRNA after 8h, comparable to monocytes (7x), but significantly
stronger than HUVEC (1.5x).
In contrast to HUVEC, EPC activate naïve CD4/CD45RA T cells. Stimulation of PHAactivated
naïve T cells with EPC resulted in a stimulation index of 380, similar to
monocytes (340), while HUVEC failed to induce such strong proliferation (30).
EPC were moreover able to present antigen in a HLA-DR restricted way. The peptide 85
B MTB was effectively presented to DR3A3 hybridoma, a cell line specifically recognizing
this peptide presented via HLA-DR. After preincubation of EPC with 85 B MTB, IL-2
production of the hybridoma was 20fold increased.
In conclusion, although EPC exhibit endothelial-like surface markers, functional
characteristics place these cells more in a monocytic lineage. This is further supported
by tests of antigen-presentation in which EPC resemble APCs more than actual
endothelial cells. These findings will pertain to the use of endothelial precursors
especially in a transplant setting.