title: Effect of treatment of latent tuberculosis infection on the T cell response to Mycobacterium tuberculosis antigens.
abstract: Most cases of latent tuberculosis infection (LTBI) do not cause symptoms during the lifetime of the infected person. Longitudinal analysis of the immune response of healthy Mycobacterium tuberculosis-infected people might, therefore, give insight into the basis of protective immunity. In a longitudinal study, we documented the effect that treatment had on the T cell response to M. tuberculosis antigens in 33 healthy people with LTBI. Preventive treatment of LTBI resulted in a 1.8-fold average increase in the numbers of interferon (IFN)- gamma -producing T cells within 26 +/- 4 days (P = .006), followed by a decrease by the end of the treatment period (82 +/- 6 days; P = .004). There was no significant overall change in the T cell response to any antigen in a control group (n = 8) of patients who elected radiological follow-up. Using live M. tuberculosis strain H37Rv as a stimulant in an enzyme-linked immunospot assay in sensitized individuals, we showed that isoniazid, but not rifampin, led to an increase in the number of IFN- gamma -producing cells. These results suggest that the integrity of the bacterial cell wall is important for M. tuberculosis in avoiding immune recognition by T cells and favor a dynamic model of LTBI.
authors.affiliation: Wellcome Trust Center for Research in Clinical Tropical Medicine, Division of Medicine, Imperial College London, Wright Fleming Institute, UK. r.j.wilkinson@imperial.ac.uk
authors.forename: Katalin A
authors.initials: KA
authors.lastname: Wilkinson
authors.forename: Onn M
authors.initials: OM
authors.lastname: Kon
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Newton
authors.forename: Graeme
authors.initials: G
authors.lastname: Meintjes
authors.forename: Robert N
authors.initials: RN
authors.lastname: Davidson
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Pasvol
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wilkinson
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology*; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000627:therapeutic use; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007538:Isoniazid / Q000008:administration & dosage / Q000627:therapeutic use; D008137:Longitudinal Studies; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology; D012293:Rifampin / Q000008:administration & dosage / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome; D014376:Tuberculosis / Q000188:drug therapy* / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D000995:Antitubercular Agents; C072681:Mycobacterium tuberculosis antigens; D007371:Interferon-gamma; D007538:Isoniazid; D012293:Rifampin