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.