Influenza A virus-specific multifunctional memory T cells show functional superiority

Westerhof, Lotus Maria (2024) Influenza A virus-specific multifunctional memory T cells show functional superiority. PhD thesis, University of Glasgow.

Abstract

Cytokine production by memory T cells is very important for T cell mediated protection. Particularly multifunctional memory T cells that produce multiple cytokines have been associated with protection. However, we currently have a limited understanding of how and when these multifunctional memory T cells are generated, and of their persistence during memory cell maintenance and secondary responses. We investigated Influenza A virus-specific CD4 and CD8 T cells using a mouse model. We found that, CD4 T cells detected using MHCII tetramers declined in lymphoid and non-lymphoid organs, but we found similar numbers of cytokine producing CD4 T cells at days 9 and 30 in the lymphoid organs. In comparison to primary responding T cells, an increased proportion of memory T cells tended to produce multiple cytokines simultaneously. Analysis of the timing of release of cytokine by influenza virus-specific T cells demonstrated that primary responding CD4 T cells from lymphoid organs were unable to produce a sustained cytokine response. In contrast CD8 T cells, memory CD4 T cells, and primary responding CD4 T cells from the lung produced a sustained cytokine response throughout the restimulation period. We found an enhanced survival signature in T
cells capable of producing multiple cytokines. Following re-infection, multifunctional T cells expressed low levels of the proliferation marker, Ki67, while cells that only produce the anti viral cytokine, interferon γ, were more likely to be Ki67+. Despite this, multifunctional memory T cells formed a substantial fraction of the secondary memory pool. Together, these data suggest that memory CD4 T cells display superior cytokine responses compared to primary responding cells, and indicate that survival rather than proliferation may dictate which populations persist within the memory pool.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Subjects: Q Science > QR Microbiology > QR180 Immunology; Q Science > QR Microbiology > QR355 Virology
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Supervisor's Name: MacLeod, Dr. Megan
• Date of Award: 2024
• Depositing User: Theses Team
• Unique ID: glathesis:2024-84175
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 28 Mar 2024 14:55
• Last Modified: 28 Mar 2024 15:00
• Thesis DOI: 10.5525/gla.thesis.84175
• URI: https://theses.gla.ac.uk/id/eprint/84175