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Generation of recombinant canine interleukin-15 and evaluation of its effects on the proliferation and function of canine NK cells.
- Source :
-
Veterinary Immunology & Immunopathology . May2015, Vol. 165 Issue 1/2, p1-13. 13p. - Publication Year :
- 2015
-
Abstract
- Interleukin-15 (IL-15) is a pleiotropic cytokine that plays a pivotal role in both innate and adaptive immunity. IL-15 is also a promising cytokine for treating cancer. Despite the growing importance of the clinical use of IL-15 for immunotherapy, no attempts have been made to generate a recombinant canine IL-15 (rcIL-15) and to examine its effects on the antitumor activities of immune effector cells in dogs. Here, we generated an rcIL-15 protein consisting of Asn-49–Ser-162 with a C-terminal His tag and examined its functions ex vivo in terms of the proliferation and antitumor effects on canine non-B, non-T, large granular natural killer (NK) cells. Non-B, non-T, large granular NK cells rapidly expanded in response to stimulation with rcIL-15 in the presence of IL-2, and a majority of the cells that selectively expanded over 21 days exhibited a CD3 − CD5 − CD4 − CD8 +/− CD21 − phenotype. Purified rcIL-15 significantly enhanced the expansion rate of canine NK cells derived from peripheral blood mononuclear cells compared to human IL-15, or culture in the absence of IL-15 for 21 days ( p < 0.05). Purified rcIL-15 was superior at enhancing the effector function of NK cells compared to human IL-15. The cytotoxic activity against canine thyroid adenocarcinoma (CTAC) cells, interferon-γ production, and the mRNA expression levels of perforin and granzyme B of expanded NK cells cultured with rcIL-15 were significantly elevated compared to those cultured with human IL-15 or without IL-15 ( p < 0.05). Intravenous administration of rcIL-15 significantly increased the numbers of lymphocytes in the peripheral blood of dogs on days 6, 8, and 11 after injection compared to numbers before administration ( p < 0.05). The results of this study suggest that the rcIL-15 protein, consisting of Asn-49–Ser-162, enhanced the proliferation and antitumor effects of canine NK cells and promoted the generation of lymphocytes in dogs. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01652427
- Volume :
- 165
- Issue :
- 1/2
- Database :
- Academic Search Index
- Journal :
- Veterinary Immunology & Immunopathology
- Publication Type :
- Academic Journal
- Accession number :
- 102313453
- Full Text :
- https://doi.org/10.1016/j.vetimm.2015.04.002