Overexpression of interleukin-15 prevents the development of murine retrovirus-induced acquired immunodeficiency syndrome.
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-gamma production by T cells stimulated with anti-T cell receptor cross-linking, and increased susceptibility to Mycobacterium bovis infection, were prevented in IL-15 Tg mice inoculated with LP-BM5 MuLV. Cytotoxic T lymphocyte response to a highly antigenic 10-mer peptide 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
Masayuki
M
Laboratory of Host Defense, Research Institute for Disease Mechanism and Control, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
Nishimura
Hitoshi
H
Yajima
Toshiki
T
Wajjwalk
Worawid
W
Matsuguchi
Testuya
T
Takahashi
Masahide
M
Nishiyama
Yukihiro
Y
Makino
Masahiko
M
Nagai
Yoshiyuki
Y
Yoshikai
Yasunobu
Y
D000818:Animals; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D009052:Leukemia Virus, Murine; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016183:Murine Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000401:mortality / Q000517:prevention & control*; D009164:Mycobacterium Infections / Q000276:immunology; D009163:Mycobacterium bovis / Q000276:immunology; D013163:Splenomegaly / Q000473:pathology; D015996:Survival Rate; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology; D013997:Time Factors
D019409:Interleukin-15