Journal
SCANDINAVIAN JOURNAL OF IMMUNOLOGY
Volume 69, Issue 2, Pages 119-129Publisher
WILEY
DOI: 10.1111/j.1365-3083.2008.02197.x
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Funding
- National Key Basic Research Programs [2007CB512406]
- National 863 Programs [2006AA02Z495]
- Arthritis Research Campaign
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Presentation in trans by the Interleukin-15 receptor alpha chain (IL-15R alpha) has been suggested as the main mechanism for IL-15 anchoring to the cell surface, but it is also evident that IL-15 can exist as a transmembrane protein. We herein demonstrate that replacement of the first 41 residues of human IL-15 (hIL-15) with Ig kappa chain leader sequence resulted in secretion of most of the recombinant hIL-15 expressed in transfectant cells, thus identifying the transmembrane region of IL-15. A fusion protein (hIL-15R alpha-Fc) between the extracellular domain of hIL-15R alpha and the Fc fragment of IgG1 was prepared and shown to be able to bind with transmembrane IL-15 (tmIL-15). The level of tmIL-15 expression in macrophages, activated T cells and B cells from 6-month-old BXSB male mice, an animal model for systemic lupus erythematosus (SLE), was significantly increased compared with that from BXSB females or young males. In addition, hIL-15R alpha-Fc was able to block the T cell stimulating and anti-apoptotic effect of the tmIL-15-positive BXSB macrophages in vitro. Intravenous administration of hIL-15R alpha-Fc reduced the titre of autoantibodies against dsDNA and also proteinuria in aged BXSB males, implying that neutralization of IL-15 activity in vivo may be an effective way of treating SLE.
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