Local immune response to respiratory syncytial virus infection is diminished in senescence-accelerated mice.
The effect of ageing on the local defence system against respiratory syncytial virus (RSV) infection was investigated using an aged mouse model of the senescence-accelerated mouse (SAM) strain P1. Following intranasal infection with RSV, SAM-P1 mice showed a marked loss in weight, with elevated virus growth in the lungs and prolonged virus shedding. The increased susceptibility to RSV infection was associated mainly with diminished cellular immunity by local virus-specific cytotoxic T lymphocytes and natural killer cells. The deficiency in cellular immune responses was due to a lack of clonal expansion of CD4(+) and CD8(+) T lymphocytes, together with an imbalance of T-helper type 1 (Th1)/Th2 cytokine production in the respiratory tract, including the lungs. Furthermore, the production of virus-specific local IgA antibody was restrained. Prolonged virus loading in the lungs of SAM-P1 mice caused a massive infiltration of CD16(+)/32(+) inflammatory cells, which was one factor responsible for severe pneumonia. The adoptive transfer of immune-competent spleen cells achieved an appreciable protection for SAM-P1 mice against RSV challenge infection. These results suggested that age-related immune dysfunction, especially defects in cellular immune responses, accounts for the increased morbidity and mortality in RSV infection of the elderly.
Liu
Beixing
B
Department of Immunology, China Medical University College of Basic Medical Sciences, Shenyang 110001, China.|Department of Microbiology, Fukui University School of Medicine, Fukui 910-1193, Japan.
Kimura
Yoshinobu
Y
Department of Medical Technology, Gifu University of Medical Science, Gifu 501-3892, Japan.|Department of Microbiology, Fukui University School of Medicine, Fukui 910-1193, Japan.
D019264:Adoptive Transfer; D019588:Aging, Premature; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D007694:Killer Cells, Natural / Q000145:classification / Q000276:immunology*; D008168:Lung / Q000821:virology*; D051379:Mice; D008817:Mice, Mutant Strains; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology* / Q000302:isolation & purification; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000914:Antibodies, Viral; D016207:Cytokines