Activation of EphA receptors on CD4+CD45RO+ memory cells stimulates migration.
We have demonstrated previously that binding of ephrin-A1 to EphA receptors on human CD4(+) and CD8(+) T cells stimulates migration. Two EphA receptors have been reported in T cells: EphA1 at the protein level and EphA4 at the mRNA level. In this study, we wanted to investigate the expression profile of these receptors in T cell subpopulations and to test if expression differences would affect the potential of cells to migrate upon ephrin-A1 binding. We have generated an anti-EphA4 mAb for expression analysis. Our data show that functional EphA4 is expressed on the cell surface of CD4(+) and CD8(+) T cells. In addition, EphA4 receptor expression is induced after overnight incubation in serum-free medium, in particular, on CD4(+)CD45RO(+) T cells. Migration of CD4(+) T cells in response to ephrin-A1 is observed for memory cells (CD45RO(+)) and much weaker for naïve cells (CD45RA(+)). A signaling complex associated with the EphA4 receptor has also been isolated and includes EphA1, the Src family kinases Fyn and Lck, Slp76, and Vav1. To conclude, T cells express EphA1 and EphA4 receptors. Expression differences of EphA4 are observed in subpopulations of CD4(+) T cells. This is related to the cell migration potential after ephrin-A1 binding.
Department of Medical Genetics, Ullevaal University Hospital, Kirkeveien 166, 0407 Oslo, Norway.
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Holen
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Nustad
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Aasheim
D000818:Animals; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002465:Cell Movement; D002478:Cells, Cultured; D036382:Ephrin-A1 / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009101:Multiple Myeloma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D036082:Receptor, EphA1 / Q000378:metabolism*; D036122:Receptor, EphA4 / Q000378:metabolism*; D015398:Signal Transduction
D036382:Ephrin-A1; D036082:Receptor, EphA1; D036122:Receptor, EphA4; D017493:Leukocyte Common Antigens