Investigating memory CD4 T cell heterogeneity using influenza A virus infection model

 

Supervisor: Dr Megan MacLeod, School of Infection & Immunity 

 

Rotation project:

Memory CD4 T cells are key co-ordinators of protective immune responses. Studies from ourselves and others are extending our understanding of the diversity of cells within the memory CD4 T cell pool (1-4). We want to investigate how this diversity impacts on memory CD4 T cell protection from subsequent infections. Understanding how CD4 T cells protect the host can provide novel insight into the design of vaccines that can protect against pathogens, especially those that can evade antibody-mediate immune control.

Influenza virus A (IAV) is an important pathogen that causes substantial morbidity and mortality across the globe. Memory CD4 T cells, particularly those that produce the inflammatory cytokine, interferon-gamma, can rapidly control the virus and recognise conserved viral regions, providing protection against multiple strains.

The aim of this mini-project is to advance our understanding of IAV specific memory CD4 T cell diversity focussing on the differences between cells that can and cannot produce cytokines. This will extend our current studies that show cytokine+ memory CD4 T cells display enhanced survival compared to cells that cannot produce cytokine (4).

The project will be split into two studies:

  1. Isolate cytokine producing and non-producing T cells for gene expression analysis at primary and memory time points
  2. Perform RNAscope on lung tissues from IAV infected mice to investigate the location of memory CD4 T cell subsets

These studies will provide training in advanced cellular and molecular techniques and generate novel data that will contribute to ongoing studies.

PhD projects in my lab will be designed in collaboration with the student and could focus on multiple aspects of immune memory, including analysis of T cells, NK cells and lung stromal cells. 

  1. Gray JI, Westerhof LM, MacLeod MKL. The roles of resident, central and effector memory CD4 T-cells in protective immunity following infection or vaccination. Immunology. 2018;154(4):574-81.
  2. Nguyen QP, Deng TZ, Witherden DA, Goldrath AW. Origins of CD4(+) circulating and tissue-resident memory T-cells. Immunology. 2019;157(1):3-12.
  1. Osum KC, Jenkins MK. Toward a general model of CD4(+) T cell subset specification and memory cell formation. Immunity. 2023;56(3):475-84.
  2. Westerhof LM, Noonan J, Hargrave KE, Chimbayo ET, Cheng Z, Purnell T, et al. Enhanced survival and low proliferation marks multifunctional virus specific memory CD4 T cells. bioRxiv. 2022:2022.12.13.520219.