Multifunctional cytokine production reveals functional superiority of memory CD4 T cells

Westerhof, L. M. , McGuire, K., MacLellan, L., Flynn, A., Gray, J. I., Thomas, M., Goodyear, C. S. and MacLeod, M. K.L. (2019) Multifunctional cytokine production reveals functional superiority of memory CD4 T cells. European Journal of Immunology, 49(11), pp. 2019-2029. (doi: 10.1002/eji.201848026) (PMID:31177549) (PMCID:PMC6900100)

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Abstract

T cell protective immunity is associated with multifunctional memory cells that produce several different cytokines. Currently, our understanding of when and how these cells are generated is limited. We have used an influenza virus mouse infection model to investigate whether the cytokine profile of memory T cells is reflective of primary responding cells or skewed towards a distinct profile. We found that, in comparison to primary cells, memory T cells tended to make multiple cytokines simultaneously. Analysis of the timings 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. Moreover, memory CD4 T cells were more resistant than primary responding CD4 T cells to inhibitors that suppress T cell receptor signalling. Together, these data suggest that memory CD4 T cells display superior cytokine responses compared to primary responding cells. These data are key to our ability to identify the cues that drive the generation of protective memory CD4 T cells following infection.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Westerhof, Lotus and Macleod, Dr Megan and Gray, Joshua and Maclellan, Dr Lindsay and Goodyear, Professor Carl
Authors: Westerhof, L. M., McGuire, K., MacLellan, L., Flynn, A., Gray, J. I., Thomas, M., Goodyear, C. S., and MacLeod, M. K.L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:European Journal of Immunology
Publisher:Wiley
ISSN:0014-2980
ISSN (Online):1521-4141
Published Online:08 June 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in European Journal of Immunology 49:2019-2029
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
581051Molecular requirements for the induction of tolerance in activated and memory CD4 T cells.Megan MacLeodArthritis Research UK (ARTRESUK)19905III -IMMUNOLOGY
588861CD4INEar: Defining the cellular interactions that control the retention of and tolerance induction in CD4 T cells at inflammatory sitesMegan MacLeodEuropean Commission (EC)334430III -IMMUNOLOGY
580946MRC Doctoral Training Grant 2011-2015Mary Beth KneafseyMedical Research Council (MRC)MR/J50032X/1VPO VICE PRINCIPAL RESEARCH & ENTERPRISE