Journal article

Quantitative and qualitative iNKT repertoire associations with disease susceptibility and outcome in macaque tuberculosis infection

Andrew Chancellor, Andrew White, Anna S Tocheva, Joe R Fenn, Mike Dennis, Liku Tezera, Akul Singhania, Tim Elliott, Marc Tebruegge, Paul Elkington, Stephan Gadola, Sally Sharpe, Salah Mansour

Tuberculosis | CHURCHILL LIVINGSTONE | Published : 2017

Abstract

Correlates of immune protection that reliably predict vaccine efficacy against Mycobacterium tuberculosis (Mtb) infection are urgently needed. Invariant NKT cells (iNKTs) are CD1d-dependent innate T cells that augment host antimicrobial immunity through production of cytokines, including interferon (IFN)-γ and tumour necrosis factor (TNF)-α. We determined peripheral blood iNKT numbers, their proliferative responses and iNKT subset proportions after in vitro antigen expansion by α-galactosylceramide (αGC) in a large cohort of mycobacteria-naïve non-human primates, and macaques from Bacillus Calmette-Guerin (BCG) vaccine and Mtb challenge studies. Animals studied included four genetically dist..

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Grants

Awarded by Cancer Research UK


Awarded by National Institute for Health Research


Funding Acknowledgements

This work was supported by the Department of Health, UK. The views expressed in this publication are those of the authors and not necessarily those of the Department of Health. We thank the staff of the Biological Investigations Group at PHE Porton and the PHE macaque colonies for assistance in conducting studies and Charlotte Sarfas, Laura Sibley, Karen Gooch and Jennifer Gullick for storage of PBMC samples, Ann Rawkins, Simon Clarke for bacteriology and aerobiology support, and Emma Rayner, Graham Hall and Geoffrey Pearson for histology support. We thank Richard Jewell and Carolann McGuire for their assistance with flow cytometry (FACS facility, Faculty of Medicine, University of Southampton).