EphA and ephrin-A proteins regulate integrin-mediated T lymphocyte interactions.
Progressive interaction with other cells is critical to all aspects of T-cell biology - from migration through tissues, to recognition of antigen-presenting cells. We demonstrate a novel mechanism for regulating T lymphocyte adhesion and thus cell-cell interactions, showing that T-cell-expressed EphA and ephrin-A proteins not only regulate adhesive properties, but do so in a diametrically opposing fashion. Integrin-mediated adhesion is stimulated by ephrin-A activation, while EphA signalling is inhibitory. Increasing ephrin-A expression enhances T-cell interactions not only with purified integrin ligands but also endothelial cells, while EphA activation down-regulates these interactions. In accordance with an in vivo role for these proteins in regulating cell-cell interactions, activation of ephrin-A signalling was found to alter the trafficking of injected T lymphocytes to peripheral lymph nodes in vivo. Given the ubiquitous nature of EphA/ephrin-A expression in tissues, these proteins likely play a significant role in regulating T-cell interactions.
Sharfe
Nigel
N
Immunology and Allergy, Department of Paediatrics, Hospital for Sick Children and University of Toronto, Toronto, Ontario M5G 1X8, Canada.
Nikolic
Martina
M
Cimpeon
Lorand
L
Van De Kratts
Alison
A
Freywald
Andrew
A
Roifman
Chaim M
CM
D000818:Animals; D002448:Cell Adhesion; D002450:Cell Communication; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology; D004730:Endothelium, Vascular / Q000166:cytology; D036382:Ephrin-A1 / Q000502:physiology*; D036384:Ephrin-A3; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D036082:Receptor, EphA1 / Q000502:physiology*; D036104:Receptor, EphA2; D013601:T-Lymphocytes / Q000502:physiology*
D036382:Ephrin-A1; D036384:Ephrin-A3; D016023:Integrins; D036082:Receptor, EphA1; D036104:Receptor, EphA2