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Dynamic Antigen-specific T-Cell Responses after Point-Source Exposure to Mycobacterium tuberculosis

Tuberculosis Immunology Group, Nuffield Department of Clinical Medicine, University of Oxford, and John Radcliffe Hospital, Oxford; Department of Public Health and Epidemiology, University of Birmingham, Edgbaston, Birmingham; and Leicestershire Health Authority, Leicester, United Kingdom

Correspondence and requests for reprints should be addressed to Prof. A. Lalvani, Tuberculosis Immunology Group, Wright Fleming Institute of Infection and Immunity, Department of Respiratory Medicine, National Heart and Lung Institute, Imperial College London, Norfolk Place, London W2 1PG, UK. E-mail: ajit.lalvani{at}ndm.ox.ac.uk

Rationale: The kinetics of Mycobacterium tuberculosis–specific Th1-type T-cell responses after M. tuberculosis 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 tuberculosis 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 assay (ELISpot) to track T cells specific for two region of difference 1 (RD1) antigens, early secretory antigenic target 6 and culture filtrate protein 10, for 18 mo after cessation of tuberculosis 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 mo. 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 mo. Of the 14 untreated students, 7 were persistently ELISpot-positive (all of whom had borderline TST results), and 7 became ELISpot-negative (all but one had negative TST results) during follow-up.

Conclusions: The decrease in M. tuberculosis–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. tuberculosis–specific T cells in the untreated TST-negative contacts suggests that an acute resolving infection may occur in some contacts.

Key Words: IFN- ELISpot • infection • tuberculosis

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