Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 38, Issue 10, Pages 2678-2688Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/eji.200838250
Keywords
Cell activation; Costimulation; Costimulatory molecules; T cells
Categories
Funding
- Austrian Science Fund [FWF, P17669-B13, SFB F1816]
- Children Cancer Research Institute (CCRI) [7003]
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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.
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