E-Poster with pre-recorded video presentation Lorne Infection and Immunity 2021

Investigating the impact of helminth infection on young and aged TVM cells (#255)

Tabinda Hussain 1 , Carmel Daunt 2 , Tiffany Bouchery 2 , Nicola Harris 2 , Kylie Quinn 1 3 , Nicole La Gruta 1
  1. Dept of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia
  2. Department of Immunology and Pathology, Monash University, Melbourne, Victoria, Australia
  3. School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia

Virtual memory T cells (TVM) are antigen-naïve CD8 T cells that have undergone partial differentiation in response to common γ (γc) chain cytokine signalling. TVM cells respond more rapidly than conventional naïve CD8 T cells to antigen stimulation, thereby providing the initial wave of effector CD8 T cells and early control of bacterial and viral infections. While TVM cells comprise 20% of the naive CD8+ T cell pool in young mice, they are selectively retained with age and comprise up to 50% of all antigenically naïve CD8+ T cells in aged mice. In addition, young TVM cells are highly proliferative but aged TVM cells lose proliferative capacity and exhibit markers of senescence. Recently, it was shown that generation of the γc cytokine, IL-4, during helminth infection drove TVM cell expansion and consequently improved pathogen clearance during subsequent infectious challenge. However, it is not known whether helminth infections similarly expand and improve responses of aged TVM cells. To evaluate this, we investigated the expansion and functional changes in TVM cells in aged helminth-infected mice. Acute infection of aged mice with helminths led to negligible expansion of the TVM subset and no gain in proliferative capacity. Furthermore, there was reduced IFN-γ production by aged TVM cells after infection. Surprisingly when transferred to a young host, aged TVM cells appeared to retain proliferative capacity in response to helminth infection, although at a slightly reduced rate compared to young TVM cells. Going forward we will investigate if the cytokine environment in aged mice is less supportive of TVM proliferation. We will also explore if helminth infection in young mice has any long-term effect on TVM number and function that influences the aged immune response. This study will provide information on how early life exposure to helminths may influence T cell subsets and functionality in advanced age, which will improve our understanding of aging-related immune dysfunction.

  1. White JT, Cross EW, Burchill MA, Danhorn T, McCarter MD, Rosen HR, et al. Virtual memory T cells develop and mediate bystander protective immunity in an IL- 15-dependent manner. Nature communications. 2016;7:11291.
  2. Quinn KM, Fox A, Harland KL, Russ BE, Li J, Nguyen THO, et al. Age-Related Decline in Primary CD8(+) T Cell Responses Is Associated with the Development of Senescence in Virtual Memory CD8(+) T Cells. Cell reports. 2018;23(12):3512-24.
  3. Rolot M, Dougall AM, Chetty A, Javaux J, Chen T, Xiao X, et al. Helminth-induced IL-4 expands bystander memory CD8(+) T cells for early control of viral infection. Nature communications. 2018;9(1):4516.
  4. Lin JS, Mohrs K, Szaba FM, Kummer LW, Leadbetter EA, Mohrs M. Virtual memory CD8 T cells expanded by helminth infection confer broad protection against bacterial infection. Mucosal immunology. 2019;12(1):258-64