Signalling via CD70, a member of the TNF family, regulates T cell functions.
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.
García
Pilar
P
DCEXS, Universitat Pompeu Fabra, Dr. Aiguader 80, 08003-Barcelona, Spain.
De Heredia
Agustín Beltrán
AB
Bellón
Teresa
T
Carpio
Emilio
E
Llano
Manuel
M
Caparrós
Esther
E
Aparicio
Pedro
P
López-Botet
Miguel
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology*; D015153:Blotting, Western; D053282:CD27 Ligand; D019556:COS Cells; D002118:Calcium / Q000378:metabolism; D002522:Chlorocebus aethiops; D003432:Cross-Linking Reagents; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology*; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D011233:Precipitin Tests; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D053282:CD27 Ligand; C505771:CD70 protein, human; D003432:Cross-Linking Reagents; D016207:Cytokines; D008565:Membrane Proteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D020928:Mitogen-Activated Protein Kinases; D002118:Calcium