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Human lung fibroblasts present bacterial antigen to autologous lung T helper cells

Human lung fibroblasts present bacterial antigen to autologous lung T helper cells
Human lung fibroblasts present bacterial antigen to autologous lung T helper cells
Lung fibroblasts are key structural cells that reside in the submucosa where they are in contact with large numbers of CD4+ T helper cells. During severe viral infection and chronic inflammation the submucosa is susceptible to bacterial invasion by lung microbiota such as Nontypeable Haemophilus influenzae (NTHi). Given their proximity in tissue, we hypothesised that human lung fibroblasts play an important role in modulating T helper cell responses to NTHi. We demonstrate that fibroblasts express the critical CD4+ T cell antigen-presentation molecule HLA-DR within the human lung, and that this expression can be recapitulated in vitro in response to interferon (IFN)?. Furthermore, we observed that cultured lung fibroblasts could internalize live NTHi. While unable to express CD80 and CD86 in response to stimulation, fibroblasts expressed the co-stimulatory molecules 4-1BBL, OX-40L and CD70, all of which are related to memory T cell activation and maintenance. CD4+ T cells isolated from the lung were predominantly (mean 97.5%) CD45RO+ memory cells. Finally, cultured fibroblasts activated IFN? and IL-17A cytokine production by autologous, NTHi-specific lung CD4+ T cells, and cytokine production was inhibited by a HLA-DR blocking antibody. These results indicate a novel role for human lung fibroblasts in contributing to responses against bacterial infection through activation of bacteria-specific CD4+ T cells.
0022-1767
110-118
Hutton, Andrew J.
1b19a9ff-f942-4e5a-a2ff-62e2c84d2328
Polak, Marta E.
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Spalluto, C. Mirella
6802ad50-bc38-404f-9a19-40916425183b
Wallington, Joshua C.
7f2909e0-96f1-4237-b2c2-ea3aa695a9d1
Pickard, Christopher
4d8b8c85-8118-4a54-b737-360344ab6e40
Staples, Karl J.
e0e9d80f-0aed-435f-bd75-0c8818491fee
Warner, Jane A.
8571b049-31bb-4a2a-a3c7-4184be20fe25
Wilkinson, Tom M.A.
8c55ebbb-e547-445c-95a1-c8bed02dd652
Hutton, Andrew J.
1b19a9ff-f942-4e5a-a2ff-62e2c84d2328
Polak, Marta E.
e0ac5e1a-7074-4776-ba23-490bd4da612d
Spalluto, C. Mirella
6802ad50-bc38-404f-9a19-40916425183b
Wallington, Joshua C.
7f2909e0-96f1-4237-b2c2-ea3aa695a9d1
Pickard, Christopher
4d8b8c85-8118-4a54-b737-360344ab6e40
Staples, Karl J.
e0e9d80f-0aed-435f-bd75-0c8818491fee
Warner, Jane A.
8571b049-31bb-4a2a-a3c7-4184be20fe25
Wilkinson, Tom M.A.
8c55ebbb-e547-445c-95a1-c8bed02dd652

Hutton, Andrew J., Polak, Marta E., Spalluto, C. Mirella, Wallington, Joshua C., Pickard, Christopher, Staples, Karl J., Warner, Jane A. and Wilkinson, Tom M.A. (2017) Human lung fibroblasts present bacterial antigen to autologous lung T helper cells. The Journal of Immunology, 198 (1), 110-118. (doi:10.4049/jimmunol.1600602). (PMID:27895174)

Record type: Article

Abstract

Lung fibroblasts are key structural cells that reside in the submucosa where they are in contact with large numbers of CD4+ T helper cells. During severe viral infection and chronic inflammation the submucosa is susceptible to bacterial invasion by lung microbiota such as Nontypeable Haemophilus influenzae (NTHi). Given their proximity in tissue, we hypothesised that human lung fibroblasts play an important role in modulating T helper cell responses to NTHi. We demonstrate that fibroblasts express the critical CD4+ T cell antigen-presentation molecule HLA-DR within the human lung, and that this expression can be recapitulated in vitro in response to interferon (IFN)?. Furthermore, we observed that cultured lung fibroblasts could internalize live NTHi. While unable to express CD80 and CD86 in response to stimulation, fibroblasts expressed the co-stimulatory molecules 4-1BBL, OX-40L and CD70, all of which are related to memory T cell activation and maintenance. CD4+ T cells isolated from the lung were predominantly (mean 97.5%) CD45RO+ memory cells. Finally, cultured fibroblasts activated IFN? and IL-17A cytokine production by autologous, NTHi-specific lung CD4+ T cells, and cytokine production was inhibited by a HLA-DR blocking antibody. These results indicate a novel role for human lung fibroblasts in contributing to responses against bacterial infection through activation of bacteria-specific CD4+ T cells.

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Accepted/In Press date: 28 October 2016
e-pub ahead of print date: 28 November 2016
Published date: 1 January 2017
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 402167
URI: https://eprints.soton.ac.uk/id/eprint/402167
ISSN: 0022-1767
PURE UUID: fb36b623-977b-4b07-bbb7-3268f06775a5
ORCID for Karl J. Staples: ORCID iD orcid.org/0000-0003-3844-6457

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Date deposited: 02 Nov 2016 16:08
Last modified: 26 Nov 2019 01:44

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