Angiogenesis-inflammation cross-talk: vascular endothelial growth factor is secreted by activated T cells and induces Th1 polarization.
Vascular endothelial growth factor (VEGF) and its receptors are critical in angiogenesis. The main player in the secretion and response to VEGF is the endothelial cell. We initiated this study to test whether T cells can secrete VEGF and are able to respond to it. Here we show that VEGF is secreted by T cells on stimulation by specific Ag or by IL-2 and by hypoxia; thus, activated T cells might enhance angiogenesis. Hypoxia also induced the expression in T cells of VEGFR2, suggesting that T cells might also respond to VEGF. Indeed, VEGF augmented IFN-gamma and inhibited IL-10 secretion by T cells responding to mitogen or Ag; thus, VEGF can enhance a Th1 phenotype. Encephalitogenic T cells stimulated in the presence of VEGF caused more severe and prolonged encephalomyelitis. Thus, T cells can play a role in angiogenesis by delivering VEGF to inflammatory sites, and VEGF can augment proinflammatory T cell differentiation.
Mor
Felix
F
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
Quintana
Francisco J
FJ
Cohen
Irun R
IR
D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D002999:Clone Cells; D016207:Cytokines / Q000096:biosynthesis*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D005260:Female; D000860:Hypoxia / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D007376:Interleukin-2 / Q000502:physiology; D008213:Lymphocyte Activation; D009389:Neovascularization, Pathologic / Q000276:immunology* / Q000473:pathology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis / Q000235:genetics
D000276:Adjuvants, Immunologic; D016207:Cytokines; D018836:Inflammation Mediators; D007376:Interleukin-2; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2