Westerhof, L. M., Noonan, J., Hargrave, K. E., Chimbayo, E. T., Cheng, Z., Purnell, T., Jackson, M. R. , Borcherding, N. and MacLeod, M. K.L. (2023) Multifunctional cytokine production marks influenza A virus specific CD4 T cells with high expression of survival molecules. European Journal of Immunology, 53(11), 2350559. (doi: 10.1002/eji.202350559) (PMID:37490492)
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Abstract
Cytokine production by memory T cells is a key mechanism of T cell mediated protection. However, we have limited understanding of the persistence of cytokine producing T cells during memory cell maintenance and secondary responses. We interrogated antigen-specific CD4 T cells using a mouse influenza A virus infection model. While CD4 T cells detected using MHCII tetramers declined in lymphoid and non-lymphoid organs, we found similar numbers of cytokine+ CD4 T cells at days 9 and 30 in the lymphoid organs. CD4 T cells with the capacity to produce cytokines expressed higher levels of pro-survival molecules, CD127 and Bcl2, than non-cytokine+ cells. Transcriptomic analysis revealed a heterogenous population of memory CD4 T cells with three clusters of cytokine+ cells. These clusters match flow cytometry data and reveal an enhanced survival signature in 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 indicate that survival rather than proliferation may dictate which populations persist within the memory pool.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Chimbayo, Elizabeth Tchaiwe and Jackson, Dr Mark and Macleod, Dr Megan and Hargrave, Dr Kerrie |
| Creator Roles: | Hargrave, K.Investigation, Formal analysis, Writing – review and editing Chimbayo, E. T.Investigation, Formal analysis, Writing – review and editing Jackson, M.Formal analysis, Writing – review and editing Macleod, M.Supervision, Project administration, Funding acquisition, Conceptualization, Investigation, Formal analysis, Visualization, Writing – original draft, Writing – review and editing |
| Authors: | Westerhof, L. M., Noonan, J., Hargrave, K. E., Chimbayo, E. T., Cheng, Z., Purnell, T., Jackson, M. R., Borcherding, N., and MacLeod, M. K.L. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Research Centre: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology |
| Journal Name: | European Journal of Immunology |
| Publisher: | Wiley |
| ISSN: | 0014-2980 |
| ISSN (Online): | 1521-4141 |
| Published Online: | 25 July 2023 |
| Copyright Holders: | Copyright © 2023 The Authors |
| First Published: | First published in European Journal of Immunology 53(11): 2350559 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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