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.

T cell fitness determined by signal strength / A. Gett, F. Sallusto, A. Lanzavecchia, J. Geginat. - In: NATURE IMMUNOLOGY. - ISSN 1529-2908. - 4:4(2003), pp. 355-360. [10.1038/ni908]

T cell fitness determined by signal strength

J. Geginat
Ultimo
Writing – Original Draft Preparation
2003

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.
in-vivo; cross-presentation; effector function; dendritic cells; self-antigens; memory cells; naive; differentiation; receptor; expression
Settore MED/04 - Patologia Generale
2003
Article (author)
File in questo prodotto:
File Dimensione Formato  
ni908.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 685.91 kB
Formato Adobe PDF
685.91 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/730337
Citazioni
  • ???jsp.display-item.citation.pmc??? 159
  • Scopus 404
  • ???jsp.display-item.citation.isi??? 392
social impact