Journal of Leukocyte Biology
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(Journal of Leukocyte Biology. 2004;76:263-270.)
© 2004 by Society for Leukocyte Biology

Signalling via CD70, a member of the TNF family, regulates T cell functions

Pilar García*, Agustín Beltrán de Heredia{dagger}, Teresa Bellón*, Emilio Carpio{dagger}, Manuel Llano*, Esther Caparrós{dagger}, Pedro Aparicio{dagger} and Miguel López-Botet*,1

* Molecular Immunopathology Unit, DCEXS, Universitat Pompeu Fabra, Barcelona, Spain; and
{dagger} Department of Biochemistry and Immunology, Facultad de Medicina, Universidad de Murcia, Spain

1Correspondence: Molecular Immunopathology Unit, DCEXS, Universitat Pompeu Fabra, Dr. Aiguader 80, 08003-Barcelona, Spain. E-mail: miguel.lopez-botet{at}upf.edu

In the present work, we provide data supporting that CD70, a tumor necrosis factor (TNF)-related molecule, defined as the CD27 ligand (CD27L), may actively regulate T cell functions similarly to other members of the TNF family (i.e., CD40L and CD30L). Cross-linking CD70 with specific monoclonal antibodies (mAb) stimulated cytotoxicity and cytokine production in human T cell clones. Detection of intracellular-free calcium mobilization and mitogen-activated protein kinase phosphorylation upon mAb engagement of CD70 further supported an active signaling role for the TNF-related molecule. Similar results were obtained in the Jurkat leukaemia T cell line stably transfected with CD70; in that system, induction of Akt phosphorylation was detected, indirectly revealing the involvement of the phosphatidylinositol-3 kinase pathway. Stimulation of CD70+ Jurkat cells, with a CD70-specific mAb or with COS-7 cells transiently transfected with CD27, induced transcriptional activity detectable by different reporter gene expression systems. Altogether, our data point out that a reciprocal communication may be established between CD27+ and CD70+ cells during the immune response.

Key Words: CD27L • T lymphocyte • NK cell • signal transduction • cytotoxicity • human




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