Abstract
Although previous studies have demonstrated delayed viral clearance and blunted effector T cell responses in aged mice during infection, memory CD8 T cells and especially secondary responses have received less attention. In this study, we show that modest differences in the number of memory CD8 T cells formed in aged versus young animals were associated with altered memory CD8 T cell differentiation. Aged immune mice had increased morbidity and mortality upon secondary viral challenge, suggesting changes in T cell immunity. Indeed, virus-specific memory CD8 T cells from aged mice showed substantially reduced proliferative expansion upon secondary infection using multiple challenge models. In addition, this defect in recall capacity of aged memory CD8 T cells was cell-intrinsic and persisted upon adoptive transfer into young mice. Thus, the poor proliferative potential of memory T cells and altered memory CD8 T cell differentiation could underlie age-related defects in antiviral immunity.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adoptive Transfer
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Aging / genetics
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Aging / immunology*
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Animals
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / pathology
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CD8-Positive T-Lymphocytes / transplantation
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CD8-Positive T-Lymphocytes / virology*
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Cell Differentiation / immunology
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Cell Line
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Cell Proliferation*
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Cytotoxicity Tests, Immunologic
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Dogs
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Epitopes, T-Lymphocyte / genetics
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Epitopes, T-Lymphocyte / immunology
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Genetic Predisposition to Disease
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Immunodominant Epitopes / genetics
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Immunodominant Epitopes / immunology
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Immunologic Memory* / genetics
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Lymphocytic Choriomeningitis / immunology
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Lymphocytic Choriomeningitis / pathology
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Lymphocytic Choriomeningitis / physiopathology
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Lymphocytic choriomeningitis virus / genetics
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Lymphocytic choriomeningitis virus / immunology*
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Mice
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Mice, Inbred C57BL
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Orthomyxoviridae / genetics
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Orthomyxoviridae / immunology*
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Orthomyxoviridae Infections / immunology
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Orthomyxoviridae Infections / pathology
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Orthomyxoviridae Infections / physiopathology
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / pathology
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T-Lymphocyte Subsets / transplantation
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T-Lymphocyte Subsets / virology
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Vaccinia virus / genetics
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Vaccinia virus / immunology
Substances
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Epitopes, T-Lymphocyte
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Immunodominant Epitopes