ePoster Presentation 49th Annual Scientific Meeting of the Australian and New Zealand Society for Immunology 2021

Comprehensive transcriptional analysis of the CD4+ memory compartments in Tconv and Treg (#279)

Holly A Withers 1 2 , Christopher M Hope 2 3 , Cheryl Y Brown 1 2 , Simon C Barry 1 2 3
  1. Biological Sciences, University of Adelaide, Adelaide, SA, Australia
  2. Department of Paediatrics, University of Adelaide, Adelaide, SA, Australia
  3. Department of Gastroenterology, Women's and Children's Hospital, North Adelaide, SA, Australia

Immunological memory is a critical feature of the adaptive immune system. Durable memory responses are necessary to mount sustained, secondary defences against pathogens and is the basis for vaccination. However, dysregulation of immunological memory can spawn destructive autoimmune reactions and drive poor disease outcomes of chronic viral infection, such as COVID-19.

CD4+ T cells are central to all adaptive immune responses as they govern the functions of surrounding cells. They are a diverse population of cells comprising proinflammatory T conventional cells (Tconv) and FOXP3+ suppressive regulatory T cells (Treg). Gene expression in Tconv and Treg must be stringently regulated to achieve immune balance and avoid immunopathology.

Tconv and Treg primarily exist in four memory stages: Naïve (TN), Central Memory (TCM), Effector Memory (TEM) and CD45RA+ Effector Memory (TemRA). TemRA are a relatively rare, ill-defined subtype, described as being terminally-differentiated and functionally heterogenous. However, recent literature highlights a significant role of Tconv TemRA in viral clearance and tumour cytotoxicity.1 The Treg memory compartments remain uncharacterised.

We performed bulk RNA-seq in Tconv and Treg memory subsets from buffy coats of healthy individuals (N = 5). Trait association analysis (via WGCNA) highlighted distinct transcriptional signatures, which effectively delineated all cellular phenotypes. Interestingly, we observed significant enrichment of a NK-cell gene signature in Tconv and Treg TemRA, compared with other cell types. Strikingly, GSEA between Tconv and Treg TemRA revealed enrichment of a Treg TemRA signature in Chronic lymphocytic leukemia patients, whilst Tconv TemRA genes were enriched in healthy patients, suggesting a possible cytolytic role of Tconv TemRA against neoplastic cells.

Currently, the Tconv and Treg memory compartments are being isolated from the peripheral blood of convalescent (12 weeks post-infection) COVID-19 patients for bulk RNA-seq to investigate whether COVID-19 infection leads to dysregulation of memory T cell gene signatures, particularly in TemRA.

  1. Tian, Y, Babor, M, Lane, J, Schulten, V, Patil, VS, et al. 2017, 'Unique phenotypes and clonal expansions of human CD4 effector memory T cells re-expressing CD45RA', Nature Communications, vol. 8, article 1473.