Differential regulation of T-cell growth by IL-2 and IL-15.
Although interleukin 2 (IL-2) and IL-15 signal through the common gamma chain (gammac) and through IL-2 receptor beta-chain (CD122) subunits, they direct distinct physiologic and immunotherapeutic responses in T cells. The present study provides some insight into why IL-2 and IL-15 differentially regulate T-cell function by revealing that these cytokines are strikingly distinct in their ability to control protein synthesis and T-cell mass. IL-2 and IL-15 are shown to be equivalent mitogens for antigen-stimulated CD8(+) T cells but not for equivalent growth factors. Antigen-primed T cells cannot autonomously maintain amino acid incorporation or de novo protein synthesis without exogenous cytokine stimulation. Both IL-2 and IL-15 induce amino acid uptake and protein synthesis in antigen-activated T cells; however, the IL-2 response is strikingly more potent than the IL-15 response. The differential action of IL-2 and IL-15 on amino acid uptake and protein synthesis is explained by temporal differences in signaling induced by these 2 cytokines. Hence, the present results show that cytokines that are equivalent mitogens can have different potency in terms of regulating protein synthesis and cell growth.
Cornish
Georgina H
GH
Cancer Research UK, London, England.
Sinclair
Linda V
LV
Cantrell
Doreen A
DA
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D019409:Interleukin-15 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D008934:Mitogens / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology*
D019409:Interleukin-15; D007376:Interleukin-2; D008934:Mitogens