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Original Article

^a Laboratory of Host Defense & Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Nagoya 466, Japan
^b Laboratory of Transgenic Animals, Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Kumamoto 862, Japan
^c Ontario Cancer Institute, Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, Ontario, Canada, M5G 2M9
Laboratory of Host Defense & Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Nagoya 466-8550, Japan.81-52-744-244981-52-744-2447

nishihit{at}med.nagoya-u.ac.jp

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 (CD44^high Ly6C⁺) of CD8⁺ T cells in the LN. These mice showed resistance to Salmonella infection accompanied by the enhanced interferon (IFN)- 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- production upon TCR engagement. The alternative IL-15 transgenic mice were susceptible to Salmonella accompanied by impaired production of endogenous IL-15 and IFN-. 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.

Key Words: transgenic mice • memory T cells • CD8 T cells • Th1/Th2 • Salmonella

© 2000 The Rockefeller University Press

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This article has been cited by other articles:

• Brewer, G. (2001). Misregulated Posttranscriptional Checkpoints: Inflammation and Tumorigenesis. JEM 193: f1-f4 [Full Text]  

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