The capacity of the TNF family members 4-1BBL, OX40L, CD70, GITRL, CD30L and LIGHT to costimulate human T cells.
Activating signals generated by members of the tumour necrosis factor receptor superfamily upon interaction with their cognate ligands play important roles in T-cell responses. Members of the tumour necrosis factor family namely 4-1BBL, OX40L, CD70, GITRL, LIGHT and CD30L have been described to function as costimulatory molecules by binding such receptors on T cells. Using our recently described system of T-cell stimulator cells we have performed the first study where all these molecules have been assessed and compared regarding their capacity to costimulate proliferation and cytokine production of human T cells. 4-1BBL, which we found to be the most potent molecule in this group, was able to mediate sustained activation and proliferation of human T cells. OX40L and CD70 were also strong inducers of T-cell proliferation, whereas the costimulatory capacity of human GITRL was significantly lower. Importantly CD30L and LIGHT consistently failed to act costimulatory on human T cells, and we therefore suggest that these molecules might be functionally distinct from the costimulatory members of this family.
Kober
Johanna
J
Institute of Immunology, Center for Physiology, Pathophysiology and Immunology, Medical University of Vienna, Vienna, Austria.
Leitner
Judith
J
Klauser
Christoph
C
Woitek
Ramona
R
Majdic
Otto
O
Stöckl
Johannes
J
Herndler-Brandstetter
Dietmar
D
Grubeck-Loebenstein
Beatrix
B
Reipert
Birgit M
BM
Pickl
Winfried F
WF
Pfistershammer
Katharina
K
Steinberger
Peter
P
D053330:4-1BB Ligand / Q000276:immunology / Q000378:metabolism; D053282:CD27 Ligand / Q000276:immunology / Q000378:metabolism; D053285:CD30 Ligand / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D006801:Humans; D008213:Lymphocyte Activation; D053278:OX40 Ligand / Q000276:immunology / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000276:immunology / Q000378:metabolism; D048069:Tumor Necrosis Factors / Q000276:immunology* / Q000378:metabolism
D053330:4-1BB Ligand; D053282:CD27 Ligand; D053285:CD30 Ligand; C505771:CD70 protein, human; D053278:OX40 Ligand; D018124:Receptors, Tumor Necrosis Factor; C505914:TNFSF14 protein, human; C478967:TNFSF18 protein, human; C089251:TNFSF4 protein, human; C505774:TNFSF8 protein, human; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D048069:Tumor Necrosis Factors