Impaired protection against Mycobacterium bovis bacillus Calmette-Guerin infection in IL-15-deficient mice.
To investigate the potential role of endogenous IL-15 in mycobacterial infection, we examined protective immunity in IL-15-deficient (IL-15(-/-)) mice after infection with Mycobacterium bovis bacillus Calmette-Guérin (BCG) or recombinant OVA-expressing BCG (rBCG-OVA). IL-15(-/-) mice exhibited an impaired protection in the lung on day 120 after BCG infection as assessed by bacterial growth. CD4(+) Th1 response capable of producing IFN-gamma was normally detected in spleen and lung of IL-15(-/-) mice on day 120 after infection. Although Ag-specific CD8 responses capable of producing IFN-gamma and exhibiting cytotoxic activity were detected in the lung on day 21 after infection with rBCG-OVA, the responses were severely impaired on days 70 and 120 in IL-15(-/-) mice. The degree of proliferation of Ag-specific CD8(+) T cells in IL-15(-/-) mice was similar to that in wild-type mice during the course of infection with rBCG-OVA, whereas sensitivity to apoptosis of Ag-specific CD8(+) T cells significantly increased in IL-15(-/-) mice. These results suggest that IL-15 plays an important role in the development of long-lasting protective immunity to BCG infection via sustaining CD8 responses in the lung.
Saito
Kimika
K
Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Yajima
Toshiki
T
Kumabe
Shino
S
Doi
Takehiko
T
Yamada
Hisakata
H
Sad
Subash
S
Shen
Hao
H
Yoshikai
Yasunobu
Y
D000818:Animals; D000941:Antigens / Q000276:immunology; D002455:Cell Division; D002465:Cell Movement; D002478:Cells, Cultured; D004527:Egg Proteins / Q000494:pharmacology; D019409:Interleukin-15 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000166:cytology / Q000382:microbiology; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009163:Mycobacterium bovis / Q000276:immunology* / Q000502:physiology; D010047:Ovalbumin / Q000494:pharmacology; D010446:Peptide Fragments; D013154:Spleen / Q000166:cytology / Q000382:microbiology; D014376:Tuberculosis / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control*
D000941:Antigens; D004527:Egg Proteins; D019409:Interleukin-15; C110366:OVA-8; D010446:Peptide Fragments; D010047:Ovalbumin