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Overexpression of interleukin‐15 prevents the development of murine retrovirus‐induced acquired immunodeficiency syndrome
Author(s) -
Umemura Masayuki,
Nishimura Hitoshi,
Yajima Toshiki,
Wajjwalk Worawid,
Matsuguchi Testuya,
Takahashi Masahide,
Nishiyama Yukihiro,
Makino Masahiko,
Nagai Yoshiyuki,
Yoshikai Yasunobu
Publication year - 2002
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0274com
Subject(s) - murine leukemia virus , retrovirus , biology , immunodeficiency , virology , immunology , spleen , microbiology and biotechnology , cytotoxic t cell , transgene , immune system , virus , gene , in vitro , genetics
LP‐BM5 murine leukemia virus (MuLV) infection causes murine acquired immunodeficiency syndrome (MAIDS), a disease characterized by varied functional abnormalities of immunocompetent cells. We found that MAIDS progression was severely retarded in IL‐15 transgenic (Tg) mice constructed with cDNA encoding secretable IL‐15 under the control of an MHC class I promoter. Several immune defects, including impaired natural killer activity, depressed IFN‐' production by T cells stimulated with anti‐T cell receptor cross‐linking, and increased susceptibility to Mycobacteium bovis infection, were prevented in IL‐15 Tg mice inoculated with LP‐BM5 MuLV. Cytotoxic T lymphocyte response to a highly antigenic 10‐mer pep‐tide encoded by LP‐BM5‐defective virus gag p12 gene was detected in the spleen and peritoneal exudate cells from IL‐15 Tg mice infected with LP‐BM5 MuLV. Intramuscular injection of cDNA encoding secretable IL‐15 also prevented the development of MAIDS. These results indicate that IL‐15 prevents the progression of MAIDS and may provide insight into an immunotherapeutic approach using the IL‐15 gene for controlling retrovirus‐induced immunodeficiency.—Umemura, M., Nishimura, H., Yajima, T., Wajjwalk, W., Matsuguchi, T., Takahashi, M., Nishiyama, Y., Makino, M., Nagai, Y., Yoshikai, Y. Overexpression of interleukin‐15 prevents the development of murine retrovirus‐induced acquired immunodeficiency syndrome. FASEB J . 16, 1755–1763 (2002)