Dynamic antigen-specific T-cell responses after point-source exposure to Mycobacterium tuberculosis.
BACKGROUND
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-gamma 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.


RESULTS
The treated TST-positive students had an average 68% decline in frequencies of RD1-specific IFN-gamma-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.
Ewer
Katie
K
Tuberculosis Immunology Group, Nuffield Department of Clinical Medicine, University of Oxford, UK.
Millington
Kerry A
KA
Deeks
Jonathan J
JJ
Alvarez
Lydia
L
Bryant
Gerry
G
Lalvani
Ajit
A
D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology; D016358:Contact Tracing; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000302:isolation & purification; D013601:T-Lymphocytes / Q000276:immunology*; D014374:Tuberculin Test; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000635:transmission
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C117940:CFP-10 protein, Mycobacterium tuberculosis; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D000939:Epitopes; D007371:Interferon-gamma