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{Day:2018:10.3389/fimmu.2018.01995,
author = {Day, CL and Abrahams, DA and Bunjun, R and Stone, L and de, Kock M and Walzl, G and Wilkinson, RJ and Burgers, WA and Hanekom, WA},
doi = {10.3389/fimmu.2018.01995},
journal = {Frontiers in Immunology},
title = {PD-1 expression on mycobacterium tuberculosis-specific CD4 T cells is associated with bacterial load in human tuberculosis},
url = {http://dx.doi.org/10.3389/fimmu.2018.01995},
volume = {9},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Persistent antigen stimulation in chronic infections has been associated with antigen-specific T cell dysfunction and upregulation of inhibitory receptors, including programmed cell death protein 1 (PD-1). Pulmonary tuberculosis (TB) disease is characterized by high levels of Mycobacterium tuberculosis (Mtb), yet the relationship between bacterial load, PD-1 expression, and Mtb-specific T cell function in human TB has not been well-defined. Using peripheral blood samples from adults with LTBI and with pulmonary TB disease, we tested the hypothesis that PD-1 expression is associated with bacterial load and functional capacity of Mtb-specific T cell responses. We found that PD-1 was expressed at significantly higher levels on Th1 cytokine-producing Mtb-specific CD4 T cells from patients with smear-positive TB, compared with smear-negative TB and LTBI, which decreased after completion of anti-TB treatment. By contrast, expression of PD-1 on Mtb-specific CD8 T cells was significantly lower than on Mtb-specific CD4 T cells and did not differ by Mtb infection and disease status. In vitro stimulation of PBMC with Mtb antigens demonstrated that PD-1 is induced on proliferating Mtb-specific CD4 T cells and that Th1 cytokine production capacity is preferentially maintained within PD-1+ proliferating CD4 T cells, compared with proliferating Mtb-specific CD4 T cells that lack PD-1 expression. Together, these data indicate that expression of PD-1 on Mtb-specific CD4 T cells is indicative of mycobacterial antigen exposure and identifies a population of effector cells with Th1 cytokine production capacity. These studies provide novel insights into the role of the PD-1 pathway in regulating CD4 and CD8 T cell responses in Mtb infection and provide rationale for future studies to evaluate PD-1 expression on antigen-specific CD4 T cells as a potential biomarker for bacterial load and treatment response in human TB.
AU  - Day,CL
AU  - Abrahams,DA
AU  - Bunjun,R
AU  - Stone,L
AU  - de,Kock M
AU  - Walzl,G
AU  - Wilkinson,RJ
AU  - Burgers,WA
AU  - Hanekom,WA
DO  - 10.3389/fimmu.2018.01995
PY  - 2018///
SN  - 1664-3224
TI  - PD-1 expression on mycobacterium tuberculosis-specific CD4 T cells is associated with bacterial load in human tuberculosis
T2  - Frontiers in Immunology
UR  - http://dx.doi.org/10.3389/fimmu.2018.01995
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000443258500001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/63095
VL  - 9
ER  -
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