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Aging (Albany NY). 2016 Nov 9;8(12):3272-3297. doi: 10.18632/aging.101105.

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.

Author information

1
Wistar Institute, Philadelphia, PA 19104, USA.
2
Present Address: The Children's Hospital of Philadelphia, Department of Biomedical and Health Informatics, Philadelphia, PA 19104, USA.
3
Present Address: Drexel University, School of Medicine, Philadelphia, PA 19104, USA.

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.

KEYWORDS:

BTLA/CD160; CD8+ cells; aging; gene expression; vaccination

PMID:
27922818
PMCID:
PMC5270668
DOI:
10.18632/aging.101105
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