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{Moseki:2022:10.1101/2022.07.20.500909,
author = {Moseki, RM and Barber, DL and Bruyn, ED and Shey, M and Van, der Plas H and Wilkinson, RJ and Meintjes, G and Riou, C},
doi = {10.1101/2022.07.20.500909},
title = {Phenotypic profile of <i>Mycobacterium tuberculosis</i>-specific CD4 T cell responses in HIV-positive patients who develop Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome},
url = {http://dx.doi.org/10.1101/2022.07.20.500909},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - <jats:title>ABSTRACT</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a frequent complication of co-treatment for TB and HIV-1. We characterized Mtb-specific CD4 T cell phenotype and transcription factor profile associated with the development of TB-IRIS.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We examined the role of CD4 T-cell transcription factors in a murine model of mycobacterial IRIS. In humans, we compared longitudinally on antiretroviral therapy (ART) the magnitude, activation, transcription factor profile and cytotoxic potential of Mtb-specific CD4 T cells between TB-IRIS (n=25) and appropriate non-IRIS control patients (n=18) using flow cytometry.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>In the murine model, CD4 T cell expression of Eomes, but not Tbet, was associated with experimentally induced IRIS. In patients, TB-IRIS onset was associated with the expansion of Mtb-specific IFNγ+CD4 T cells (p=0.039). TB-IRIS patients had higher HLA-DR expression (p=0.016), but no differences in the expression of T-bet or Eomes were observed. At TB-IRIS onset, Eomes+Tbet+Mtb-specific IFNγ+CD4+ T cells showed higher expression of Granzyme B in TB-IRIS patients (p=0.026).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>While the murine model of MAC-IRIS suggests that Eomes+CD4 T cells underly IRIS, TB-IRIS was not associated with Eomes expression in patients. Mtb-specific IFNγ+CD4 T cell responses in TB-IRIS patients are differentiated, highly activated and potentially cytotoxic.</jats:p></jats:sec>
AU  - Moseki,RM
AU  - Barber,DL
AU  - Bruyn,ED
AU  - Shey,M
AU  - Van,der Plas H
AU  - Wilkinson,RJ
AU  - Meintjes,G
AU  - Riou,C
DO  - 10.1101/2022.07.20.500909
PY  - 2022///
TI  - Phenotypic profile of <i>Mycobacterium tuberculosis</i>-specific CD4 T cell responses in HIV-positive patients who develop Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome
UR  - http://dx.doi.org/10.1101/2022.07.20.500909
ER  -
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