Cell-intrinsic defects in the proliferative response of antiviral memory CD8 T cells in aged mice upon secondary infection.
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.
Decman
Vilma
V
Immunology Program, The Wistar Institute, Philadelphia, PA 19104, USA.
Laidlaw
Brian J
BJ
Dimenna
Lauren J
LJ
Abdulla
Sarah
S
Mozdzanowska
Krystyna
K
Erikson
Jan
J
Ertl
Hildegund C J
HC
Wherry
E John
EJ
D019264:Adoptive Transfer; D000375:Aging / Q000235:genetics / Q000276:immunology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000637:transplantation / Q000821:virology*; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D049109:Cell Proliferation; D003601:Cytotoxicity Tests, Immunologic; D004285:Dogs; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D020022:Genetic Predisposition to Disease; D016056:Immunodominant Epitopes / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory / Q000235:genetics; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009975:Orthomyxoviridae / Q000235:genetics / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology / Q000637:transplantation / Q000821:virology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes