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

Abstract

Influenza A virus (IAV) infection leads to the formation of mucosal memory CD4 T cells that can protect the host. An in-depth understanding of the signals that shape memory cell development is required for more effective vaccine design. We have examined the formation of memory CD4 T cells in the lung following IAV infection of mice, characterizing changes to the lung landscape and immune cell composition. IAV-specific CD4 T cells were found throughout the lung at both primary and memory time points. These cells were found near lung airways and in close contact with a range of immune cells including macrophages, dendritic cells, and B cells. Interactions between lung IAV-specific CD4 T cells and major histocompatibility complex (MHC)II+ cells during the primary immune response were important in shaping the subsequent memory pool. Treatment with an anti-MHCII blocking antibody increased the proportion of memory CD4 T cells found in lung airways but reduced interferon-γ expression by IAV-specific immunodominant memory CD4 T cells. The immunodominant CD4 T cells expressed higher levels of programmed death ligand 1 (PD1) than other IAV-specific CD4 T cells and PD1+ memory CD4 T cells were located further away from MHCII+ cells than their PD1-low counterparts. This distinction in location was lost in mice treated with anti-MHCII antibodies. These data suggest that sustained antigen presentation in the lung impacts the formation of memory CD4 T cells by regulating their cytokine production and location.

People
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

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Worrell, Julie C.
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

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Pirillo, Chiara
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

Lukoszek, Radoslaw and Inesta-Vaquera, Francisco and Brett, Natasha J.M. and Liang, Shang and Hepburn, Lydia A. and Hughes, David J. and Pirillo, Chiara and Roberts, Edward W. and Cowling, Victoria H. (2024) CK2 phosphorylation of CMTR1 promotes RNA cap formation and influenza virus infection. Cell Reports, 43 (7): 114405. ISSN 2639-1856

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Brennan, Euan
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

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Masdefiol Garriga, Andreu
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

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Gray, Joshua I.
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

See full publications list
Purnell, Thomas
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

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Roberts, Ed
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

Kumar, Saumya and Basto, Afonso P. and Ribeiro, Filipa and Almeida, Silvia C.P. and Campos, Patricia and Peres, Carina and Pulvirenti, Nadia and Al-Khalidi, Sarwah and Kilbey, Anna and Tosello, Jimena and Piaggio, Eliane and Russo, Momtchilo and Gama-Carvalho, Margarida and Coffelt, Seth B. and Roberts, Ed W. and Geginat, Jens and Florindo, Helena F. and Graca, Luis (2024) Specialized Tfh cell subsets driving type-1 and type-21 humoral responses in lymphoid tissue. Cell Discovery, 10: 64. ISSN 2056-5968

Bentley-Abbot, Calum and Heslop, Rhiannon and Pirillo, Chiara and Chandrasegaran, Praveena and McConnell, Gail and Roberts, Ed and Hutchinson, Edward and MacLeod, Annette (2024) An easy to use tool for the analysis of subcellular mRNA transcript colocalisation in smFISH data. Scientific Reports, 14: 8348. ISSN 2045-2322

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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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