Effect of treatment of latent tuberculosis infection on the T cell response to Mycobacterium tuberculosis antigens.
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.
Wilkinson
Katalin A
KA
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
Kon
Onn M
OM
Newton
Sandra M
SM
Meintjes
Graeme
G
Davidson
Robert N
RN
Pasvol
Geoffrey
G
Wilkinson
Robert J
RJ
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
D000942:Antigens, Bacterial; D000995:Antitubercular Agents; C072681:Mycobacterium tuberculosis antigens; D007371:Interferon-gamma; D007538:Isoniazid; D012293:Rifampin