Poster Presentation 16th Lorne Infection and Immunity 2026

Pregnancy impacts epitope-specific CD8+ T cells directed towards acute and chronic viruses (132447)

Jennifer Habel 1 , Thi HO Nguyen 1 , E Kaitlynn Allen 2 , Shihan Li 1 , Anastasia A Minervina 2 , Mikhail V Pogorelyy 2 , Priyanka Chaurasia 3 , Celia Douros 4 , Theo Karapanagiotidis 4 , Suellen Nicholson 4 , Michael Souter 1 , Stephanie Gras 5 , Katherine Bond 4 , Deborah A Williamson 4 , Martha Lappas 6 , Sue Walker 6 , Jamie Rossjohn 3 , Jan Schroeder 1 , Jeremy C Crawford 2 , Paul G Thomas 2 , Louise C Rowntree 1 , Katherine Kedzierska 1
  1. Department of Microbiology & Immunology, University of Melbourne, Melbourne, Victoria, Australia
  2. St Jude Children's Research Hospital, Memphis, Tennessee, USA
  3. Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia
  4. Victorian Infectious Diseases Reference Laboratory, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
  5. Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria, Australia
  6. Department of Obstetrics, Gynaecology and Newborn Health, University of Melbourne, Heidelberg, Victoria, Australia

Pregnant women are at increased risk of severe respiratory virus infections like influenza and COVID-19, and re-activation of chronic viruses such as cytomegalovirus (CMV). While it is well-established that CD8+ T cells have an important role in the control and clearance of viral infections, less is known on how pregnancy impacts the establishment, phenotype and function of epitope-specific CD8+ T cells across different viruses. To address this, we performed single-cell RNAseq, CITEseq, and TCRseq on epitope-specific CD8+ T cells using peptide-HLA-I-DNA-oligo dextramers specific for influenza A virus (IAV), SARS-CoV-2, respiratory syncytial virus (RSV), Epstein-Barr virus (EBV), and CMV in pregnant and non-pregnant peripheral blood, and pregnancy-matched decidual tissue from HLA-A*02:01+ individuals. Analysis of CD8+ T cells directed towards acute respiratory viruses (IAV, SARS-CoV-2, RSV) showed lower expression of RNA encoding cytotoxic granules and inhibitory receptors during pregnancy. Meanwhile, in chronic virus-specific (EBV, CMV) CD8+ T cells, pregnant women had increased cytotoxic granule RNA expression and altered surface expression of chemokine receptors CX3CR1 and CCR5, indicating a more “effector-like” phenotype in pregnancy. Within the immunodominant epitopes A2/M158 (IAV), A2/pp65465 (CMV), and A2/BMLF1280 (EBV) we identified common T cell receptor (TCR) gene usages in pregnant and non-pregnant blood and decidua. We provide the first report of decidual IAV-specific CD8+ T cells, which had similar TCR gene usage as the respective donor-matched peripheral blood. Additional analyses into acute vs chronic virus-specific CD8+ T cells identified key gene signatures associated with each of the 5 virus specificities. Further experiments on acute and chronic virus epitope-specific CD8+ T cells from pregnant and non-pregnant women will help us better understand the mechanisms underlying the altered phenotype in pregnancy. Taken together, these data suggest that pregnancy alters CD8+ T cell immunity in a virus-specific manner and provide novel insights that reveal potential targets for immunotherapies during pregnancy.