Published ahead of print on June 23, 2006, doi:10.1164/rccm.200511-1783OC
Am. J. Respir. Crit. Care Med., Volume 174, Number 7, October 2006, 831-839
A more recent version of this article appeared on October 1, 2006
Submitted on November 21, 2005
Accepted on June 16, 2006
Dynamic Antigen-specific T Cell Responses after Point-source Exposure to Mycobacterium tuberculosis
Katie Ewer1, Kerry A Millington1, Jonathan J Deeks2, Lydia Alvarez1, Gerry Bryant3, and Ajit Lalvani1*
1 Nuffield Department of Clinical Medicine, Tuberculosis Immunology Group, University Of Oxford, Oxford, Oxon, United Kingdom,
2 Department of Public Health and Epidemiology, University of Birmingham, Edgbaston, Birmingham, United Kingdom,
3 Leicestershire Health Authority, Leicester, Leics, United Kingdom
* To whom correspondence should be addressed. E-mail: ajit.lalvani{at}ndm.ox.ac.uk.
Rationale: The kinetics of Mycobacterium tuberculosis (M.tb)-specific Th1-type T cell responses following M.tb infection are likely to be important in determining clinical outcome.
Objective: To investigate the kinetics of T cell responses, in the context of a point-source school TB outbreak, in three groups of contacts who differed by preventive treatment status and tuberculin skin test (TST) results: 38 treated TST-positive students; 11 untreated TST-positive staff and 14 untreated students with negative or borderline TST results.
Methods: We used the ex vivo IFN- enzyme-linked immunospot (ELISpot) assay to track T cells specific for the RD1 antigens, early secretory antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10), for 18 months after cessation of TB exposure.
Main Results: The treated TST-positive students had an average 68% decline in frequencies of RD1-specific IFN--secreting T cells per year (P<0.0001) and 6 of 38 students had no detectable RD1-specific T cells by 18 months. No change in frequencies of these cells was observed in the untreated TST-positive staff (P=0.38) and none were ELISpot-negative at 18 months. Of the 14 untreated students, seven were persistently ELISpot-positive (all of whom had borderline TST results), while seven became ELISpot-negative (all but one had negative TST results) during follow-up.
Conclusions: The decrease in M.tb-specific T cells and their disappearance in a proportion of treated students likely reflect declining antigenic and bacterial load in vivo induced by antibiotic treatment. The observed disappearance of M.tb-specific T cells in the untreated TST-negative contacts suggests that an acute resolving infection may occur in some contacts.
Key words: tuberculosis; infection; IFN- ELISpot
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