Oral Presentation Lorne Infection and Immunity 2022

Metabolic adaptations in ageing T cells (#16)

Kylie Quinn 1 2 , Tabinda Hussain 2 , Felix Kraus 2 , Luke Formosa 2 , Wai Lam 2 , Palak Mehta 1 , Georg Ramm 2 , Michael Ryan 2 , Nicole La Gruta 2
  1. RMIT University, BUNDOORA, VIC, Australia
  2. Monash University, Clayton

Ageing leads to the accumulation of differentiated, unconventional T cell populations. One such cell type is the virtual memory T (TVM) cell, which are semi-differentiated but antigen-naïve CD8 T cells. TVM cells have increased survival compared to conventional naïve CD8 T cells (TN) and accumulate in number with age, but become dysfunctional. Our work identified age-related shifts in T cell metabolism that did not correlate with function but may support the preferential survival of certain T cell subsets with age. With increased age, memory phenotype cells such as TVM cells exhibited increased mitochondrial load and spare respiratory capacity, despite a marked reduction in classic T cell functions (proliferation, IFNg production and cytotoxicity). In both mouse and human CD8 T cells, increased SRC was associated with heightened sensitivity to IL-15 and blocking IL-15 could reduce SRC in TVM cells. Our model suggests that IL-15 sensitivity and signalling increases in memory phenotype T cells in general and TVM cells in particular with age, to support increased SRC and cell survival. However, SRC is not a consistent positive predictor of conventional T cell function across the lifespan. In our ongoing work, we are using our model of T cell survival, function, metabolism and ageing to optimise the development of T cell-based therapies for older patients.

  1. Quinn KM, Hussain T, Kraus F, Formosa LE, Lam WK, Dagley MJ, Saunders EC, Assmus LM, Wynne-Jones E, Cooper L, Good-Jacobson KL, Kedzierska K, Mackay LK, McConville MJ, Ramm G, Ryan MT and La Gruta NL. Metabolic Characteristics of Young and Aged CD8+ T cell Subsets Do Not Predict Functionality. 2020, Nat Comms 11: 2857