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The Journal of Immunology, 2008, 180, 5141 -5148
Copyright © 2008 by The American Association of Immunologists, Inc.

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The Presence of Activated CD4+ T Cells Is Essential for the Formation of Colony-Forming Unit-Endothelial Cells by CD14+ Cells

Rachel T. van Beem*, Willy A. Noort*, Carlijn Voermans*, Marion Kleijer*, Anja ten Brinke{dagger}, S. Marieke van Ham{dagger}, C. Ellen van der Schoot1,*,{ddagger} and Jaap Jan Zwaginga*,§

* Department of Experimental Immunohematology and {dagger} Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; {ddagger} Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands; and § Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands

The number of colony forming unit-endothelial cells (CFU-EC) in human peripheral blood was found to be a biological marker for several vascular diseases. In this study, the heterogeneous composition of immune cells in the CFU-ECs was investigated. We confirmed that monocytes are essential for the formation of CFU-ECs. Also, however, CD4+ T cells were found to be indispensable for the induction of CFU-EC colonies, mainly through cell-cell contact. By blocking or activating CD3 receptors on CD4+ T cells or blocking MHC class II molecules on monocytes, it was shown that TCR-MHCII interactions are required for induction of CFU-EC colonies. Because the supernatant from preactivated T cells could also induce colony formation from purified monocytes, the T cell support turned out to be cytokine mediated. Gene expression analysis of the endothelial-like colonies formed by CD14+ cells showed that colony formation is a proangiogenic differentiation and might reflect the ability of monocytes to facilitate vascularization. This in vitro study is the first to reveal the role of TCR-MHC class II interactions between T cells and monocytes and the subsequent inflammatory response as stimulus of monocytic properties that are associated with vascularization.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 Address correspondence and reprint requests to Dr. C. E. van der Schoot, Sanquin Research, Department of Experimental Immunohematology, Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands. E-mail address: e.vanderschoot{at}sanquin.nl

2 Abbreviations used in this paper: EPC, endothelial progenitor cell; CFU-EC, CFU-endothelial cell; FN, fibronectin; acLDL, acetylated low density lipoprotein; Alexa Fluor 488 AcLDL, acLDL conjugated with Alexa Fluor 488; VEGF, vascular endothelial growth factor.




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