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.
Highlights
It is well documented that immune responses decline with age, leaving the elderly less responsive to vaccines and increasingly susceptible to infections and cancer [14]
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 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
Summary
It is well documented that immune responses decline with age, leaving the elderly less responsive to vaccines and increasingly susceptible to infections and cancer [14]. We previously demonstrated both intrinsic and extrinsic defects in CD8+ T cells of aged mice [5]. To assess the basis for these defects in CD8+ T cells from the aged and determine how they are rescued by BTLA/CD160 checkpoint blockade, we compared the global transcriptomes of CD8+ T cells from young and aged mice that had been immunized with E1-deleted adenovirus (Ad) vectors expressing the influenza A/PR8/34 virus NP.
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