Virtual memory cells make a major contribution to the response of aged influenza-naïve mice to influenza virus infection

• Main Authors: Kathleen G. Lanzer, Tres Cookenham, William W. Reiley, Marcia A. Blackman
• Format: Article
• Language: English
• Published: BMC 2018-08-01
• Series: Immunity & Ageing
• Subjects: T cell receptor repertoire; Virtual memory (VM) T cells; True memory (TM) T cells; Influenza; Ageing; Mouse model
• Online Access: http://link.springer.com/article/10.1186/s12979-018-0122-y

Abstract Background A diverse repertoire of naïve T cells is thought to be essential for a robust response to new infections. However, a key aspect of aging of the T cell compartment is a decline in numbers and diversity of peripheral naïve T cells. We have hypothesized that the age-related decline in naïve T cells forces the immune system to respond to new infections using cross-reactive memory T cells generated to previous infections that dominate the aged peripheral T cell repertoire. Results Here we confirm that the CD8 T cell response of aged, influenza-naïve mice to primary infection with influenza virus is dominated by T cells that derive from the memory T cell pool. These cells exhibit the phenotypic characteristics of virtual memory cells rather than true memory cells. Furthermore, we find that the repertoire of responding CD8 T cells is constrained compared with that of young mice, and differs significantly between individual aged mice. After infection, these virtual memory CD8 T cells effectively develop into granzyme-producing effector cells, and clear virus with kinetics comparable to naïve CD8 T cells from young mice. Conclusions The response of aged, influenza-naive mice to a new influenza infection is mediated largely by memory CD8 T cells. However, unexpectedly, they have the phenotype of VM cells. In response to de novo influenza virus infection, the VM cells develop into granzyme-producing effector cells and clear virus with comparable kinetics to young CD8 T cells.