At least two types of interleukin (IL)-15 mRNA isoforms are generated by alternative splicing at the 5′ upstream of exon 5 in mice. To elucidate the potential roles of IL-15 isoforms in immune responses in vivo, we constructed two groups of transgenic mice using originally described IL-15 cDNA with a normal exon 5 (normal IL-15 transgenic [Tg] mice) and IL-15 cDNA with an alternative exon 5 (alternative IL-15 Tg mice) under the control of an MHC class I promoter. Normal IL-15 Tg mice constitutionally produced a significant level of IL-15 protein and had markedly increased numbers of memory type (CD44high Ly6C+) of CD8+ T cells in the LN. These mice showed resistance to Salmonella infection accompanied by the enhanced interferon (IFN)-γ production, but depletion of CD8+ T cells exaggerated the bacterial growth, suggesting that the IL-15–dependent CD8+ T cells with a memory phenotype may serve to protect against Salmonella infection in normal IL-15 Tg mice. On the other hand, a large amount of intracellular IL-15 protein was detected but hardly secreted extracellularly in alternative IL-15 Tg mice. Although most of the T cells developed normally in the alternative IL-15 Tg mice, they showed impaired IFN-γ production upon TCR engagement. The alternative IL-15 transgenic mice were susceptible to Salmonella accompanied by impaired production of endogenous IL-15 and IFN-γ. Thus, two groups of IL-15 Tg mice may provide information concerning the different roles of IL-15 isoforms in the immune system in vivo.
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3 January 2000
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January 03 2000
Differential Roles of Interleukin 15 mRNA Isoforms Generated by Alternative Splicing in Immune Responses in Vivo
Hitoshi Nishimura,
Hitoshi Nishimura
aLaboratory of Host Defense & Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Nagoya 466, Japan
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Toshiki Yajima,
Toshiki Yajima
aLaboratory of Host Defense & Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Nagoya 466, Japan
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Yoshikazu Naiki,
Yoshikazu Naiki
aLaboratory of Host Defense & Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Nagoya 466, Japan
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Hironaka Tsunobuchi,
Hironaka Tsunobuchi
aLaboratory of Host Defense & Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Nagoya 466, Japan
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Masayuki Umemura,
Masayuki Umemura
aLaboratory of Host Defense & Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Nagoya 466, Japan
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Keiko Itano,
Keiko Itano
aLaboratory of Host Defense & Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Nagoya 466, Japan
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Tetsuya Matsuguchi,
Tetsuya Matsuguchi
aLaboratory of Host Defense & Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Nagoya 466, Japan
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Misao Suzuki,
Misao Suzuki
bLaboratory of Transgenic Animals, Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Kumamoto 862, Japan
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Pamela S. Ohashi,
Pamela S. Ohashi
cOntario Cancer Institute, Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, Ontario, Canada, M5G 2M9
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Yasunobu Yoshikai
Yasunobu Yoshikai
aLaboratory of Host Defense & Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Nagoya 466, Japan
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Hitoshi Nishimura
aLaboratory of Host Defense & Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Nagoya 466, Japan
Toshiki Yajima
aLaboratory of Host Defense & Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Nagoya 466, Japan
Yoshikazu Naiki
aLaboratory of Host Defense & Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Nagoya 466, Japan
Hironaka Tsunobuchi
aLaboratory of Host Defense & Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Nagoya 466, Japan
Masayuki Umemura
aLaboratory of Host Defense & Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Nagoya 466, Japan
Keiko Itano
aLaboratory of Host Defense & Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Nagoya 466, Japan
Tetsuya Matsuguchi
aLaboratory of Host Defense & Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Nagoya 466, Japan
Misao Suzuki
bLaboratory of Transgenic Animals, Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Kumamoto 862, Japan
Pamela S. Ohashi
cOntario Cancer Institute, Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, Ontario, Canada, M5G 2M9
Yasunobu Yoshikai
aLaboratory of Host Defense & Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Nagoya 466, Japan
Abbreviations used in this paper: HKS, heat killed-Salmonella; MMC, mytomycin-C; Tg, transgenic.
Received:
August 09 1999
Revision Requested:
October 13 1999
Accepted:
October 15 1999
Online ISSN: 1540-9538
Print ISSN: 0022-1007
© 2000 The Rockefeller University Press
2000
The Rockefeller University Press
J Exp Med (2000) 191 (1): 157–170.
Article history
Received:
August 09 1999
Revision Requested:
October 13 1999
Accepted:
October 15 1999
Citation
Hitoshi Nishimura, Toshiki Yajima, Yoshikazu Naiki, Hironaka Tsunobuchi, Masayuki Umemura, Keiko Itano, Tetsuya Matsuguchi, Misao Suzuki, Pamela S. Ohashi, Yasunobu Yoshikai; Differential Roles of Interleukin 15 mRNA Isoforms Generated by Alternative Splicing in Immune Responses in Vivo. J Exp Med 3 January 2000; 191 (1): 157–170. doi: https://doi.org/10.1084/jem.191.1.157
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