Influenza infection of beta 2-microglobulin-deficient (beta 2m-/-) mice reveals a loss of CD4+ T cell functions with aging.
Following influenza infection, aged mice have prolonged viral shedding that is presumably due to lower anti-influenza class I-restricted CD8+ CTL activity. To examine alternative viral clearance mechanisms in immunosenescense, we infected young (1.5-2.5 month) and aged (15-18 month) class I and CD8+-deficient beta 2m-/- mice with influenza A/Port Chalmers/1/73 (H3N2). We found that 40% of young beta 2m-/- mice were shedding virus from the lung on day 9 (mean titer of 0.3 log10 TCID[50]), with a maximal anti-influenza class II CTL activity of 68+/-2% on day 7. In contrast, 100% of aged beta 2m-/- mice were still shedding virus (mean titer of 3.0 log10 TCID[50]) from the lung on day 9 with a peak CTL activity of 15+/-6%. Aged beta 2m-/- mice also had significantly lower pulmonary IFN-gamma levels, serum anti-influenza neutralizing Ab, and anti-influenza mucosal IgA titers, as well as a less intense pulmonary inflammatory response on early days of infection. Th2-mediated cytokines were dysregulated. We conclude that there are multiple mechanisms responsible for the age-related delay in recovery from influenza. These include decreased anti-influenza class II-restricted CTL activity, pulmonary IFN-gamma levels, and serum neutralizing Ab. Taken together, these findings show a loss of CD4+ T cell functions with aging.
Taylor
S F
SF
Department of Medicine, University of Florida, College of Medicine, Gainesville 32610, USA.
Cottey
R J
RJ
Zander
D S
DS
Bender
B S
BS
D000375:Aging / Q000276:immunology*; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D007111:Immunity, Cellular; D007249:Inflammation / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000235:genetics*
D000914:Antibodies, Viral; D016207:Cytokines; D001613:beta 2-Microglobulin