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NCI: The activation of T cells requires a co-stimulatory signal with T cell receptor activation, provided in many cases by activation of CD28 in resting T cells. 4-1BB (CD137) is a member of the TNF receptor gene family that provides another T cell co-stimulatory signal. 4-1BB is expressed by activated cytotoxic and helper T cells and its expression is induced by a variety of T cell stimuli, including activation of the T cell receptor or stimulation with mitogens. The ligand for 4-1BB (4-1BBL) is induced on activated antigen-presenting cells including macrophages, activating T cells expressing 4-1BB. Mice lacking 4-1BB survive and have an altered though functional immune response. T cells of mice lacking 4-1BB proliferate more rapidly than normal T cells, but have reduced cytokine secretion. The costimulatory signal provided by 4-1BB may act in combination with CD28 activation to prolong the T cell response, and may also act independently of CD28. Stimulation of T cells with the 4-1BB ligand may provide a the
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