Imperial College London
Professor Robert Wilkinson

ProfessorRobertWilkinson

Faculty of Medicine, Department of Infectious Disease

Professor in Infectious Diseases
 
 
 
//

Contact

 

r.j.wilkinson Website

 
 
//

Location

 

Commonwealth BuildingHammersmith Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Moseki:2023:ofid/ofac546,
author = {Moseki, RM and Barber, DL and Du, Bruyn E and Shey, M and Van, der Plas H and Wilkinson, RJ and Meintjes, G and Riou, C},
doi = {ofid/ofac546},
journal = {Open Forum Infectious Diseases},
pages = {1--10},
title = {Phenotypic profile of Mycobacterium tuberculosis-specific CD4 T-cell responses in people with advanced human immunodeficiency virus who develop tuberculosis-associated immune reconstitution inflammatory syndrome},
url = {http://dx.doi.org/10.1093/ofid/ofac546},
volume = {10},
year = {2023}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND: Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a frequent complication of cotreatment for TB and human immunodeficiency virus (HIV)-1. We characterized Mycobacterium tuberculosis (Mtb)-specific CD4 T-cell phenotype and transcription factor profile associated with the development of TB-IRIS. METHODS: We examined the role of CD4 T-cell transcription factors in a murine model of mycobacterial IRIS. In humans, we used a longitudinal study design to compare the magnitude of antiretroviral therapy, 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. RESULTS: In the murine model, CD4 T-cell expression of Eomesodermin (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 = .039). Patients with TB-IRIS had higher HLA-DR expression (P = .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 patients with TB-IRIS (P = .026). CONCLUSIONS: Although the murine model of Mycobacterium avium complex-IRIS suggests that Eomes+CD4 T cells underly IRIS, TB-IRIS was not associated with Eomes expression in patients. Mycobacterium tuberculosis-specific IFNγ+CD4 T-cell responses in TB-IRIS patients are differentiated, highly activated, and potentially cytotoxic.
AU  - Moseki,RM
AU  - Barber,DL
AU  - Du,Bruyn E
AU  - Shey,M
AU  - Van,der Plas H
AU  - Wilkinson,RJ
AU  - Meintjes,G
AU  - Riou,C
DO  - ofid/ofac546
EP  - 10
PY  - 2023///
SN  - 2328-8957
SP  - 1
TI  - Phenotypic profile of Mycobacterium tuberculosis-specific CD4 T-cell responses in people with advanced human immunodeficiency virus who develop tuberculosis-associated immune reconstitution inflammatory syndrome
T2  - Open Forum Infectious Diseases
UR  - http://dx.doi.org/10.1093/ofid/ofac546
UR  - https://www.ncbi.nlm.nih.gov/pubmed/36726536
UR  - https://academic.oup.com/ofid/article/10/1/ofac546/6761821?login=true
UR  - http://hdl.handle.net/10044/1/102244
VL  - 10
ER  -
Download