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Epitope-specific CD4+, but not CD8+, T-cell responses induced by recombinant influenza A viruses protect against Mycobacterium tuberculosis infection

Flórido, Manuela, Pillay, Roman, Gillis, Caitlin M, Xia, Yingju, Turner, Stephen J., Triccas, James A., Stambas, John and Britton, Warwick J 2015, Epitope-specific CD4+, but not CD8+, T-cell responses induced by recombinant influenza A viruses protect against Mycobacterium tuberculosis infection, European journal of immunology, vol. 45, no. 3, pp. 780-793, doi: 10.1002/eji.201444954.

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Title Epitope-specific CD4+, but not CD8+, T-cell responses induced by recombinant influenza A viruses protect against Mycobacterium tuberculosis infection
Author(s) Flórido, Manuela
Pillay, Roman
Gillis, Caitlin M
Xia, Yingju
Turner, Stephen J.
Triccas, James A.
Stambas, JohnORCID iD for Stambas, John orcid.org/0000-0002-5690-2551
Britton, Warwick J
Journal name European journal of immunology
Volume number 45
Issue number 3
Start page 780
End page 793
Total pages 14
Publisher Wiley
Place of publication Weinheim, Germany
Publication date 2015-03
ISSN 1521-4141
Keyword(s) CD4+ T cells
Interferon-γ
Lung
Recombinant influenza A virus
Tuberculosis
CD4+ T cells
Science & Technology
Life Sciences & Biomedicine
Immunology
CD4(+) Tcells
Interferon-gamma
BACILLE CALMETTE-GUERIN
PULMONARY TUBERCULOSIS
VACCINIA VIRUS
CENTRAL MEMORY
VACCINATION
MUCOSAL
ANTIGEN
IMMUNITY
IMMUNIZATION
Summary Tuberculosis remains a global health problem, in part due to failure of the currently available vaccine, BCG, to protect adults against pulmonary forms of the disease. We explored the impact of pulmonary delivery of recombinant influenza A viruses (rIAVs) on the induction of Mycobacterium tuberculosis (M. tuberculosis)-specific CD4(+) and CD8(+) T-cell responses and the resultant protection against M. tuberculosis infection in C57BL/6 mice. Intranasal infection with rIAVs expressing a CD4(+) T-cell epitope from the Ag85B protein (PR8.p25) or CD8(+) T-cell epitope from the TB10.4 protein (PR8.TB10.4) generated strong T-cell responses to the M. tuberculosis-specific epitopes in the lung that persisted long after the rIAVs were cleared. Infection with PR8.p25 conferred protection against subsequent M. tuberculosis challenge in the lung, and this was associated with increased levels of poly-functional CD4(+) T cells at the time of challenge. By contrast, infection with PR8.TB10.4 did not induce protection despite the presence of IFN-γ-producing M. tuberculosis-specific CD8(+) T cells in the lung at the time of challenge and during infection. Therefore, the induction of pulmonary M. tuberculosis epitope-specific CD4(+), but not CD8(+) T cells, is essential for protection against acute M. tuberculosis infection in the lung.
Language eng
DOI 10.1002/eji.201444954
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 920108 Immune System and Allergy
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2015, Wiley
Persistent URL http://hdl.handle.net/10536/DRO/DU:30077279

Document type: Journal Article
Collection: School of Medicine
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