Imperial College London
Professor Robert Wilkinson

ProfessorRobertWilkinson

Faculty of Medicine, Department of Infectious Disease

Professor in Infectious Diseases
 
 
 
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Contact

 

r.j.wilkinson Website

 
 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Sallin:2018:10.1038/s41564-018-0231-6,
author = {Sallin, MA and Kauffman, KD and Riou, CR and Du, Bruyn E and Foreman, TW and Sakai, S and Hoft, SG and Myers, TG and Gardina, PJ and Sher, AF and Moore, R and Wilder-Kofie, T and Moore, IN and Sette, A and Lindestam, Arlehamn CS and Wilkinson, RJ and Barber, DL},
doi = {10.1038/s41564-018-0231-6},
journal = {Nature Microbiology},
pages = {1198--1205},
title = {Host resistance to pulmonary Mycobacterium tuberculosis 2 infection requires CD153 expression},
url = {http://dx.doi.org/10.1038/s41564-018-0231-6},
volume = {3},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Mycobacterium tuberculosis infection (Mtb) is the leading cause of death due to a single infectious agent and is among the top ten causes of all human deaths worldwide1. CD4 T cells are essential for resistance to Mtb infection, and for decades it has been thought that IFNγ production is the primary mechanism of CD4 T-cell-mediated protection2,3. However, IFNγ responses do not correlate with host protection, and several reports demonstrate that additional anti-tuberculosis CD4 T-cell effector functions remain unaccounted for4,5,6,7,8. Here we show that the tumour-necrosis factor (TNF) superfamily molecule CD153 (encoded by the gene Tnfsf8) is required for control of pulmonary Mtb infection by CD4 T cells. In Mtb-infected mice, CD153 expression is highest on Mtb-specific T helper 1 (TH1) cells in the lung tissue parenchyma, but its induction does not require TH1 cell polarization. CD153-deficient mice develop high pulmonary bacterial loads and succumb early to Mtb infection. Reconstitution of T-cell-deficient hosts with either Tnfsf8−/− or Ifng−/− CD4 T cells alone fails to rescue mice from early mortality, but reconstitution with a mixture of Tnfsf8−/− and Ifng−/− CD4 T cells provides similar protection as wild-type T cells. In Mtb-infected non-human primates, CD153 expression is much higher on Ag-specific CD4 T cells in the airways compared to blood, and the frequency of Mtb-specific CD153-expressing CD4 T cells inversely correlates with bacterial loads in granulomas. In Mtb-infected humans, CD153 defines a subset of highly polyfunctional Mtb-specific CD4 T cells that are much more abundant in individuals with controlled latent Mtb infection compared to those with active tuberculosis. In all three species, Mtb-specific CD8 T cells did not upregulate CD153 following peptide stimulation. Thus, CD153 is a major immune mediator of host protection against pulmonary Mtb infection and CD4 T cells are one importan
AU  - Sallin,MA
AU  - Kauffman,KD
AU  - Riou,CR
AU  - Du,Bruyn E
AU  - Foreman,TW
AU  - Sakai,S
AU  - Hoft,SG
AU  - Myers,TG
AU  - Gardina,PJ
AU  - Sher,AF
AU  - Moore,R
AU  - Wilder-Kofie,T
AU  - Moore,IN
AU  - Sette,A
AU  - Lindestam,Arlehamn CS
AU  - Wilkinson,RJ
AU  - Barber,DL
DO  - 10.1038/s41564-018-0231-6
EP  - 1205
PY  - 2018///
SN  - 2058-5276
SP  - 1198
TI  - Host resistance to pulmonary Mycobacterium tuberculosis 2 infection requires CD153 expression
T2  - Nature Microbiology
UR  - http://dx.doi.org/10.1038/s41564-018-0231-6
UR  - http://hdl.handle.net/10044/1/62804
VL  - 3
ER  -
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