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Expression in Spleen Leukocytes1,2Scottish Fish Immunology Research Centre, School of Biological Sciences, University of Aberdeen, Aberdeen, United Kingdom
IL-15 is a member of the common 
-chain family of cytokines that possess a heterogeneous repertoire of activities on various cells of the immune system. We report here the first functional characterization of a fish IL-15 in rainbow trout. The trout IL-15 gene is 6-kb long and contains six exons and five introns that transcribe into a 1.2-kb mRNA containing seven out-of-frame AUG initiation codons and translate into a 193-aa peptide. Potential sites for transcriptional activators and repressors have been identified in the trout IL-15 gene. Like IL-15 from other species, trout IL-15 is closely linked to an INPP4B gene, but there is also a BCL10 gene located between the IL-15 and INPP4B genes. Three alternative splicing variants of the trout IL-15 gene have also been identified and their expression in vivo was studied. Trout IL-15 expression is present in all the tissues and cell lines studied. Recombinant trout IFN- selectively increased IL-15 expression but had little effect on other cytokines such as IL-1
and IL-11. Recombinant trout IL-15 preferentially stimulated splenic leukocytes from healthy fish, where it induced a large increase in IFN- expression, with little, if any, effect on IL-1 expression. This effect was quite long-lived, and was still apparent 24 h poststimulation. Although the exact cell types being affected have still to be determined, it is clear that once produced IL-15 will have a profound affect on the ability of the fish immune system to activate antimicrobial defenses and genes induced themselves by IFN-.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by grants from the European Commission (Stressgenes, Q5RS-2001-002211, and Aquafirst, 513692).
2 The nucleotide sequence(s) presented in this article will appear in the EMBL/DDBJ/GenBank nucleotide sequence database under the following accession numbers: AJ555868 (IL-15 cDNA) and AJ628345 (genomic sequence for IL-15, BCL10, and partial of INPP4B gene).
3 Address correspondence and reprint requests to Prof. Christopher J. Secombes, Scottish Fish Immunology Research Centre, School of Biological Sciences, University of Aberdeen, Aberdeen AB24 2TZ, U.K. E-mail address: c.secombes{at}abdn.ac.uk
4 Abbreviations used in this paper: c, common -chain; LSP, long signal peptide; SSP, short signal peptide; UTR, untranslated region; ER, endoplasmic reticulum; rt, recombinant trout; Q-PCR, quantitative PCR; EF, elongation factor; SV, splicing variant; NLS, nuclear localization signal; EST, expressed sequence tag; -IRE, IFN--responsive element; IPTG, isopropyl -D-thiogalactoside; GR, glucocorticoid receptor.
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