Westerhof, Lotus M. and Noonan, Jonathan and Hargrave, Kerrie E. and Chimbayo, Elizabeth T. and Cheng, Zhiling and Purnell, Thomas and Jackson, Mark R. and Borcherding, Nicholas and MacLeod, Megan 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. ISSN 0014-2980

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.

People
Westerhof, Lotus M.
Author

Westerhof, Lotus M. and Noonan, Jonathan and Hargrave, Kerrie E. and Chimbayo, Elizabeth T. and Cheng, Zhiling and Purnell, Thomas and Jackson, Mark R. and Borcherding, Nicholas and MacLeod, Megan 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. ISSN 0014-2980

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Noonan, Jonathan
Author

Westerhof, Lotus M. and Noonan, Jonathan and Hargrave, Kerrie E. and Chimbayo, Elizabeth T. and Cheng, Zhiling and Purnell, Thomas and Jackson, Mark R. and Borcherding, Nicholas and MacLeod, Megan 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. ISSN 0014-2980

See full publications list
Hargrave, Kerrie E.
Author

Hargrave, Kerrie E. and Worrell, Julie C. and Pirillo, Chiara and Brennan, Euan and Masdefiol Garriga, Andreu and Gray, Joshua I. and Purnell, Thomas and Roberts, Edward W. and MacLeod, Megan K.L. (2024) Lung influenza virus specific memory CD4 T cell location and optimal cytokine production are dependent on interactions with lung antigen-presenting cells. Mucosal Immunology, 17 (5). pp. 843-857. ISSN 1933-0219

Westerhof, Lotus M. and Noonan, Jonathan and Hargrave, Kerrie E. and Chimbayo, Elizabeth T. and Cheng, Zhiling and Purnell, Thomas and Jackson, Mark R. and Borcherding, Nicholas and MacLeod, Megan 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. ISSN 0014-2980

See full publications list
Chimbayo, Elizabeth T.
Author

Westerhof, Lotus M. and Noonan, Jonathan and Hargrave, Kerrie E. and Chimbayo, Elizabeth T. and Cheng, Zhiling and Purnell, Thomas and Jackson, Mark R. and Borcherding, Nicholas and MacLeod, Megan 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. ISSN 0014-2980

See full publications list
Cheng, Zhiling
Author

Westerhof, Lotus M. and Noonan, Jonathan and Hargrave, Kerrie E. and Chimbayo, Elizabeth T. and Cheng, Zhiling and Purnell, Thomas and Jackson, Mark R. and Borcherding, Nicholas and MacLeod, Megan 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. ISSN 0014-2980

See full publications list
Purnell, Thomas
Author

Westerhof, Lotus M. and Noonan, Jonathan and Hargrave, Kerrie E. and Chimbayo, Elizabeth T. and Cheng, Zhiling and Purnell, Thomas and Jackson, Mark R. and Borcherding, Nicholas and MacLeod, Megan 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. ISSN 0014-2980

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Jackson, Mark R.
Author

Vens, C. and van Luijk, P. and Vogelius, R.I. and El Naqa, I. and Humbert-Vidan, L. and von Neubeck, C. and Gomez-Roman, N. and Bahn, E. and Brualla, L. and Böhlen, T.T. and Ecker, S. and Koch, R. and Handeland, A. and Pereira, S. and Possenti, L. and Rancati, T. and Todor, D. and Vanderstraeten, B. and Van Heerden, M. and Ullrich, W. and Jackson, M. and Alber, M. and Marignol, L. and ESTRO DREAM team (2024) A joint physics and radiobiology DREAM team vision - towards better response prediction models to advance radiotherapy. Radiotherapy and Oncology, 196: 110277. ISSN 0167-8140

Derby, Sarah and Jackson, Mark R. and Williams, Karin and Stobo, Jamie and Kelly, Caroline and Sweeting, Lorna and Shad, Shumaila and Herbert, Christopher and Short, Susan C. and Williamson, Aoife and James, Allan and Nowicki, Stefan and Bulbeck, Helen and Chalmers, Anthony (2024) Concurrent olaparib and radiotherapy in elderly patients with newly diagnosed glioblastoma: the phase I dose escalation PARADIGM trial. International Journal of Radiation Oncology, Biology, Physics, 118 (5). pp. 1371-1378. ISSN 0360-3016

Derby, Sarah and Jackson, Mark R. and Williams, Karin and Stobo, Jamie and Kelly, Caroline and Sweeting, Lorna and Shad, Shumaila and Herbert, Christopher and Short, Susan C. and Williamson, Aoife and James, Allan and Nowicki, Stefan and Bulbeck, Helen and Chalmers, Anthony J. (2024) Concurrent olaparib and radiation therapy in older patients with newly diagnosed glioblastoma: the phase 1 dose-escalation PARADIGM trial. International Journal of Radiation Oncology, Biology, Physics, 118 (5). pp. 1371-1378. ISSN 0360-3016

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Borcherding, Nicholas
Author

Westerhof, Lotus M. and Noonan, Jonathan and Hargrave, Kerrie E. and Chimbayo, Elizabeth T. and Cheng, Zhiling and Purnell, Thomas and Jackson, Mark R. and Borcherding, Nicholas and MacLeod, Megan 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. ISSN 0014-2980

See full publications list
MacLeod, Megan K.L.
Author

Hargrave, Kerrie E. and Worrell, Julie C. and Pirillo, Chiara and Brennan, Euan and Masdefiol Garriga, Andreu and Gray, Joshua I. and Purnell, Thomas and Roberts, Edward W. and MacLeod, Megan K.L. (2024) Lung influenza virus specific memory CD4 T cell location and optimal cytokine production are dependent on interactions with lung antigen-presenting cells. Mucosal Immunology, 17 (5). pp. 843-857. ISSN 1933-0219

Westerhof, Lotus M. and Noonan, Jonathan and Hargrave, Kerrie E. and Chimbayo, Elizabeth T. and Cheng, Zhiling and Purnell, Thomas and Jackson, Mark R. and Borcherding, Nicholas and MacLeod, Megan 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. ISSN 0014-2980

See full publications list
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