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Autophagy and T-cell Exhaustion

Autophagy and T-Cell exhaustion

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There's increasing evidence that there may be benefits to targeting the host. TB is very clever and it manipulates the host immune system to its own advantage, so if we could use drugs to help the immune system, then we may be able to make it more effective.

Ken Smith, Professor of Medicine and Head of Department of Medicine.  “It might be that exhausted T cells can’t fight multi-drug resistant TB effectively, in which case we need to find a way to overcome this exhaustion and spur the T cells on to rid the body of the disease” 

This is the approach that Professors Ken Smith and Andres Floto from the Department of Medicine, are taking. Ken Smith is looking at the role that specialist immune cells known as T cells play in the persistence of multi-drug resistant strains of TB. His group has evidence that around two thirds of the population have T cells which have a tendency to become ‘exhausted’ when activated.



1. Thomas DC, Clare S, Sowerby JM, Pardo M, Juss JK, Goulding DA, van der Weyden L, Storisteanu D, Prakash A, Espéli M, Flint S, Lee JC, Hoenderdos K, Kane L, Harcourt K, Mukhopadhyay S, Umrania Y, Antrobus R, Nathan JA, Adams DJ, Bateman A, Choudhary JS, Lyons PA, Condliffe AM, Chilvers ER, Dougan G and Smith KGC (2017). “Eros is a novel transmembrane protein that controls the phagocyte respiratory burst and is essential for innate immunity.” J Exp Med. 214(4):1111-1128. doi: 10.1084/jem.20161382

2. Lee JC, Biasci D, Roberts R, Gearry RB, Mansfield JC, Ahmad T, Prescott NJ, Satsangi J, Wilson DC, Jostins L, Anderson CA; UK IBD Genetics Consortium., Traherne JA, Lyons PA, Parkes M and Smith KGC (2017). “Genome-wide association study identifies distinct genetic contributions to prognosis and susceptibility in Crohn’s disease.” Nat Genet. 49(2):262-268. doi: 10.1038/ng.3755

3. Peters JE, Lyons PA, Lee JC, Richard AC, Fortune MD, Newcombe PJ, Richardson S and Smith KGC (2016). “Insight into genotype-phenotype associations through eQTL mapping in multiple cell types in health and immune-mediated disease.” PLoS Genet.12(3):e1005908. doi: 10.1371/journal.pgen.1005908

4. Linterman, MA, Denton, AE, Divekar, DP, Zvetkova, I, Kane, L, Ferreira, C, Veldhoen, M, Clare, S, Dougan G, Espéli, M, and Smith, KGC(2014). CD28 expression is required after T cell priming for helper T cell responses and protective immunity to infection. ELIFE, 3. doi:10.7554/eLife.03180

5. Wallin , EF, Jolly, EC, Suchánek, O, Bradley, JA, Espéli, M, Jayne, DRW, Linterman, MA, and Smith, KGC (2014). Human T follicular helper and T follicular regulatory cell maintenance is independent of germinal centers. Blood, 124(17), 2666-74. doi:10.1182/blood-2014-07-585976

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Professor Ken Smith's Group

The Centre supports collaborative partnerships and scientific training activities in basic biomedical and health-related research. This is achieved through coordinated cross-faculty research across departments and research institutes in Cambridge including The Wellcome Trust Sanger Institute