Cutting edge: Vascular endothelial growth factor-mediated signaling in human CD45RO+ CD4+ T cells promotes Akt and ERK activation and costimulates IFN-gamma production.
In this study, we find that CD45RO+ memory populations of CD4+ T lymphocytes express the vascular endothelial growth factor (VEGF) receptors KDR and Flt-1 at both the mRNA and protein levels. Furthermore, by Western blot analysis, we find that VEGF increases the phosphorylation and activation of ERK and Akt within CD4+CD45RO+ T cells. These VEGF-mediated signaling responses were inhibited by a KDR-specific small interfering RNA in a VEGF receptor-expressing Jurkat T cell line and by SU5416, a pharmacological KDR inhibitor, in CD4+CD45RO+ T cells. We also find that VEGF augments mitogen-induced production of IFN-gamma in a dose-dependent manner (p < 0.001) and significantly (p < 0.05) increases directed chemotaxis of this T cell subset. Collectively, our results for the first time define a novel function for VEGF and KDR in CD45RO+ memory T cell responses that are likely of great pathophysiological importance in immunity.
Basu
Aninda
A
Transplantation Research Center and the Division of Nephrology, Department of Medicine, Children's Hospital Boston, MA 02115, USA.
Hoerning
Andre
A
Datta
Dipak
D
Edelbauer
Monika
M
Stack
Maria P
MP
Calzadilla
Katiana
K
Pal
Soumitro
S
Briscoe
David M
DM
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D002633:Chemotaxis; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis*; D019169:Jurkat Cells; D017493:Leukocyte Common Antigens; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000032:analysis / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis* / Q000235:genetics / Q000502:physiology
D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D007371:Interferon-gamma; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D051057:Proto-Oncogene Proteins c-akt; D020929:Mitogen-Activated Protein Kinase Kinases; D017493:Leukocyte Common Antigens