Modulation of NKG2D Expression in Human CD8(+) T Cells Corresponding with Tuberculosis Drug Cure.


Hassan, SS; Cho, JE; Akram, M; Fielding, KL; Dockrell, HM; Cliff, JM; (2013) Modulation of NKG2D Expression in Human CD8(+) T Cells Corresponding with Tuberculosis Drug Cure. PLoS One, 8 (7). e70063. ISSN 1932-6203 DOI: 10.1371/journal.pone.0070063

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Abstract

BACKGROUND Biomarkers predicting tuberculosis treatment response and cure would facilitate drug development. This study investigated expression patterns of the co-stimulation molecule NKG2D in human tuberculosis and treatment to determine its potential usefulness as a host biomarker of tuberculosis drug efficacy. METHODS Tuberculosis patients (n = 26) were recruited in Lahore, Pakistan, at diagnosis and followed up during treatment. Household contacts (n = 24) were also recruited. NKG2D expression was measured by qRT-PCR in RNA samples both ex vivo and following overnight mycobacterial stimulation in vitro. Protein expression of NKG2D and granzyme B was measured by flow cytometry. RESULTS NKG2D expression in newly diagnosed tuberculosis patients was similar to household contacts in ex vivo RNA, but was higher following in vitro stimulation. The NKG2D expression was dramatically reduced by intensive phase chemotherapy, in both ex vivo blood RNA and CD8(+) T cell protein expression, but then reverted to higher levels after the continuation phase in successfully treated patients. CONCLUSION The changes in NKG2D expression through successful treatment reflect modulation of the peripheral cytotoxic T cell response. This likely reflects firstly in vivo stimulation by live Mycobacterium tuberculosis, followed by the response to dead bacilli, antigen-release and finally immunopathology resolution. Such changes in host peripheral gene expression, alongside clinical and microbiological indices, could be developed into a biosignature of tuberculosis drug-induced cure to be used in future clinical trials.

Item Type: Article
Faculty and Department: Academic Services & Administration > Academic Administration
Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Faculty of Infectious and Tropical Diseases > Dept of Clinical Research
Research Centre: TB Centre
Tropical Epidemiology Group
PubMed ID: 23922903
Web of Science ID: 322838900138
URI: http://researchonline.lshtm.ac.uk/id/eprint/1126713

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