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Blood, 15 July 2006, Vol. 108, No. 2, pp. 600-608.
Prepublished online as a Blood First Edition Paper on April 4, 2006; DOI 10.1182/blood-2005-12-4827.
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IMMUNOBIOLOGY
Differential regulation of T-cell growth by IL-2 and IL-15
Georgina H. Cornish,
Linda V. Sinclair, and
Doreen A. Cantrell
From Cancer Research UK, London, England; the Edward Jenner Institute for Vaccine Research, Berkshire, England; and the School of Life Sciences, University of Dundee, Scotland.
Although interleukin 2 (IL-2) and IL-15 signal through the common gamma chain ( c) and through IL-2 receptor  –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.
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