BD Science Communication Session Presentation 49th Annual Scientific Meeting of the Australian and New Zealand Society for Immunology 2021

Depletion of TVM cells with LCMV infection leads to selective retention of more functional, less senescent cells (#4)

Tabinda Hussain 1 , Angela Nguyen 1 , Daniel Thiele 1 , Ee Shan Pang 1 , Meredith O'Keeffe 1 , Kim Good-Jacobson 1 , Kylie Quinn 2 , Nicole La Gruta 1
  1. Dept of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia
  2. School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia

TVM cells are semi-differentiated CD8 T cells that develop from Eomeshi thymic precursors due to strong reactivity to self-ligands. In the periphery, TVM cells are dependent on IL-15, IL-4, type I IFNs and CD8α+ DCs. TVM cells respond more rapidly than naïve CD8 T cells to antigen stimulation, providing early control of viral and bacterial infections. TVM cells comprise 20% of the naive CD8 T cell pool in young mice, but they are selectively retained with age, comprising 50% of all antigenically naïve CD8 T cells in aged mice while expressing markers of senescence and losing proliferative capacity. It is known that LCMV infects DCs and also induces a rapid type I IFN response. As both of these are factors that regulate the TVM cell population, therefore we aimed to understand how LCMV infection affects the TVM subset. We found a marked depletion (>3-fold) of TVM cells after infection with LCMV-WE acute strain. The depletion in TVM subset was maintained for several weeks and the remaining TVM cells were phenotypically distinct from those in uninfected mice, with reduced expression of Eomes and CD122 (IL-15Rβ), both considered to be classical TVM markers. Functionally, the surviving TVM cells proliferated more robustly after TCR stimulation in vitro. To determine whether these LCMV driven changes had a lasting impact on the TVM subset into old age, we aged mice (infected with LCMV when young) out to 18-20 months. We found that the TVM cell numbers had not fully recovered, retained lower expression of Eomes and CD122 with downregulation of senescence markers, such as phospho-MAPK, compared to naïve aged controls. Collectively these data suggest that LCMV infection induces a depleted but more responsive subset of TVM cells which goes on to exhibit an attenuated senescence phenotype in aged mice.