Poster Presentation Lorne Infection and Immunity 2019

High spare respiratory capacity is a key feature of virtual memory CD8 T cells, which is augmented by age, infection and IL-15 signaling. (#170)

Kylie Quinn 1 , Felix Kraus 1 , Luke Formosa 1 , Michael Dagley 2 , Eleanor Saunders 2 , Tabinda Hussain 1 , Malcolm McConville 2 , Michael Ryan 1 , Nicole La Gruta 1
  1. Biomedical Discovery Institute, Monash University, Clayton, VIC, Australia
  2. Department of Biochemistry, University of Melbourne, Parkville, VIC, Australia

Virtual memory T (TVM) cells are antigen-naïve CD8 T cell cells that have undergone IL-15-driven semi-differentiation in the periphery. They exhibit some characteristics that are classically associated with conventional memory (TMEM) cells, such as accelerated TCR-driven proliferation and enhanced IL-15 responsiveness compared to “true naïve” (TN) cells. Recently, high spare respiratory capacity (SRC) was proposed as a metabolic characteristic of TMEM cells that promotes their longevity and functionality. We sought to determine if TVM cells also exhibited high SRC but, in contrast to previous reports, we found that high SRC was a feature of TVM cells rather than TMEM cells and SRC increased substantially with age. We had previously shown that TVM cells become dysfunctional with age but exhibited a survival advantage, which illustrated that SRC does not necessarily correlate with function but may correlate with survival. We then hypothesised that IL-15 production drove high SRC and survival in TVM cells. When parameters associated with IL-15 signalling were assessed, such as receptor (CD122) expression, STAT5 phosphorylation and expression of the anti-apoptotic protein Bcl-2, these parameters were substantially higher in young TVM cells as compared to TN and TMEM cells and they increased with age. IL-15 knockout mice illustrated that IL-15 was essential for TVM cell development at all ages but it did not impact TMEM cell frequency in aged mice. Collectively, these data highlight that high SRC is more accurately described as feature of TVM cells, likely reflecting their sensitivity to IL-15 signaling which drives metabolic remodeling and survival.