title: Defective CD8 T cell responses in aged mice are due to quantitative and qualitative changes in virus-specific precursors.
abstract: Aging is associated with suboptimal CD8 T cell responses to viral infections. It is not clear whether these poor responses are due to environmental influences or quantitative and qualitative changes in the pool of responding CD8 T cells. Our studies demonstrated several deleterious age-related changes in the pool of Ag-specific CD8 T cells that respond to infection. The majority of CD8 T cells from uninfected aged mice was CD44(Hi) and had increased expression of inhibitory receptors including PD1, LAG3, 2B4, and CD160. These aged CD44(Hi) CD8 T cells were transcriptionally similar to exhausted CD8 T cells found during chronic infections. In addition, the number of virus-specific precursors in aged mice prior to infection was decreased up to 10-fold, and many of these Ag-specific precursors had high expression of CD44 and PD1. Finally, TCR transgenic studies demonstrated that the CD44(Hi) Ag-specific CD8 T cells from unimmunized aged and young mice were qualitatively inferior compared with CD44(Lo) CD8 T cells from aged or young donors. Thus, a decrease in precursor frequency as well as qualitative changes of CD8 T cells during aging are directly related to impaired immunity.
authors.affiliation: Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Vilma
authors.initials: V
authors.lastname: Decman
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Laidlaw
authors.forename: Travis A
authors.initials: TA
authors.lastname: Doering
authors.forename: Jin
authors.initials: J
authors.lastname: Leng
authors.forename: Hildegund C J
authors.initials: HC
authors.lastname: Ertl
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Goldstein
authors.forename: E John
authors.initials: EJ
authors.lastname: Wherry
mesh_terms: D000375:Aging / Q000276:immunology*; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D001117:Arenaviridae Infections / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D005260:Female; D058851:GPI-Linked Proteins / Q000096:biosynthesis; D018960:Hyaluronan Receptors / Q000032:analysis; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity; D051379:Mice; D061026:Programmed Cell Death 1 Receptor / Q000096:biosynthesis; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism; D011971:Receptors, Immunologic / Q000096:biosynthesis; D000071176:Signaling Lymphocytic Activation Molecule Family; D000093322:Lymphocyte Activation Gene 3 Protein
chemical_list: D015703:Antigens, CD; C511585:Cd160 protein, mouse; C490007:Cd244a protein, mouse; D058851:GPI-Linked Proteins; D018960:Hyaluronan Receptors; D061026:Programmed Cell Death 1 Receptor; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family; D000093322:Lymphocyte Activation Gene 3 Protein