title: Age-related changes in the gene expression profile of antigen-specific mouse CD8+ T cells can be partially reversed by blockade of the BTLA/CD160 pathways during vaccination.
abstract: We analyzed gene expression profiles of young and aged mouse CD8+T cells specific for the nucleoprotein (NP) of influenza A/PR8/34 virus. CD8+T cells were stimulated either by the NP antigen expressed in its native form or fused into the herpes virus (HSV)-1 glycoprotein D (gD) protein, which blocks signaling through the immunoinhibitory B and T lymphocyte attenuator (BTLA) and CD160 pathways. We show that NP-specific CD8+T cells from aged mice exhibit numerous differences in gene expression compared to NP-specific CD8+T cells from young mice, including a significant reduction of expression in genes involved in T cell receptor (TcR) and CD28 signaling. We also show that these changes can be reversed in a sub-population (~50%) of the aged mice by a BTLA/CD160 checkpoint blockade. These results suggest that BTLA/CD160 checkpoint blockade has potential value as a vaccine additive to induce better CD8+T cell responses in the aged.
authors.affiliation: Wistar Institute, Philadelphia, PA 19104, USA.|Present Address: The Children's Hospital of Philadelphia, Department of Biomedical and Health Informatics, Philadelphia, PA 19104, USA.
authors.forename: Noor
authors.initials: N
authors.lastname: Dawany
authors.affiliation: Wistar Institute, Philadelphia, PA 19104, USA.|Present Address: Drexel University, School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Parzych
authors.affiliation: Wistar Institute, Philadelphia, PA 19104, USA.
authors.forename: Louise C
authors.initials: LC
authors.lastname: Showe
authors.affiliation: Wistar Institute, Philadelphia, PA 19104, USA.
authors.forename: Hildegund Cj
authors.initials: HC
authors.lastname: Ertl
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology*; D009980:Influenza A virus; D007252:Influenza Vaccines / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D059467:Transcriptome / Q000502:physiology*; D014611:Vaccination
chemical_list: D015703:Antigens, CD; C488868:BTLA protein, mouse; C511585:Cd160 protein, mouse; D058851:GPI-Linked Proteins; D007252:Influenza Vaccines; D011971:Receptors, Immunologic
keywords: BTLA/CD160; CD8+ cells; aging; gene expression; vaccination