Differential roles of interleukin 15 mRNA isoforms generated by alternative splicing in immune responses in vivo

Hitoshi Nishimura, Toshiki Yajima, Yoshikazu Naiki, Hironaka Tsunobuchi, Masayuki Umemura, Keiko Itano, Tetsuya Matsuguchi, Misao Suzuki, Pamela S. Ohashi, Yasunobu Yoshikai

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    128 Citations (Scopus)

    Abstract

    At least two types of interleukin (IL)-I 5 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 rising 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)-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.

    Original languageEnglish
    Pages (from-to)157-169
    Number of pages13
    JournalJournal of Experimental Medicine
    Volume191
    Issue number1
    DOIs
    Publication statusPublished - Jan 3 2000

    All Science Journal Classification (ASJC) codes

    • Immunology and Allergy
    • Immunology

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