T cell fitness determined by signal strength - PubMed (original) (raw)
doi: 10.1038/ni908. Epub 2003 Mar 17.
Affiliations
- PMID: 12640450
- DOI: 10.1038/ni908
T cell fitness determined by signal strength
Amanda V Gett et al. Nat Immunol. 2003 Apr.
Abstract
Two potential outcomes confront proliferating antigen-stimulated naive T cells: differentiation to effector and memory cells, or deletion. How stimulation affects cell fate is unclear. Autonomous CD8+ T cell differentiation has been proposed, but this does not explain the abortive proliferation of T cells induced by immature dendritic cells. Here we show that human and mouse CD4+ and CD8+ T cells receiving short or weak stimulation of the T cell receptor proliferate in response to interleukin 2 (IL-2) but are not 'fit' because they die by neglect, fail to proliferate in response to IL-7 and IL-15 and disappear in vivo. Conversely, prolonged or strong stimulation promotes 'fitness' by enhancing survival and cytokine responsiveness. Our results are consistent with the concept that signal strength drives progressive T cell differentiation and the acquisition of fitness.
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