Peptide-specific T cell response to Mycobacterium tuberculosis: clinical spectrum, compartmentalization, and effect of chemotherapy.
The T cell repertoire of 59 patients with untreated tuberculosis was compared with that of 46 bacille Calmette-Guérin-vaccinated controls by assaying the proliferative responses to six permissively recognized peptides from the 16-, 19-, and 38-kDa molecules of Mycobacterium tuberculosis. A trend from higher to lower reactivity following this order: vaccinated controls > lymph node disease > localized extrapulmonary > pulmonary > pleural was seen for 4 of the peptides (P < .03). The decreased response of blood lymphocytes from patients with pleural tuberculosis was partially accounted for by sequestration of peptide-responsive cells within the pleural fluid. Chemotherapy "reversed" the depressed proliferative responses of patients with pulmonary and pleural tuberculosis depending on the peptide origin, being greatest for peptides of 16 kDa, transient for those of 19 kDa, and least for those of 38 kDa. These data demonstrate antigen specificity in the decreased responsiveness of patients with tuberculosis.
Wilkinson
R J
RJ
MRC Tuberculosis and Related Infections Unit, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom. kaw10@po.cwru.edu
Vordermeier
H M
HM
Wilkinson
K A
KA
Sjölund
A
A
Moreno
C
C
Pasvol
G
G
Ivanyi
J
J
D000293:Adolescent; D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology*; D000995:Antitubercular Agents / Q000627:therapeutic use*; D001500:BCG Vaccine / Q000276:immunology; D001426:Bacterial Proteins / Q000138:chemical synthesis / Q000276:immunology*; D002455:Cell Division; D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D004977:Ethambutol / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D007538:Isoniazid / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008074:Lipoproteins; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D010996:Pleural Effusion / Q000166:cytology; D011718:Pyrazinamide / Q000627:therapeutic use; D012293:Rifampin / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology*; D014373:Tuberculin / Q000378:metabolism / Q000494:pharmacology; D014376:Tuberculosis / Q000188:drug therapy / Q000276:immunology* / Q000517:prevention & control
C087864:19 kDa antigen, Mycobacterium; C075966:Ag38 antigen, Mycobacterium tuberculosis; D000942:Antigens, Bacterial; D000995:Antitubercular Agents; D001500:BCG Vaccine; D001426:Bacterial Proteins; D018984:Epitopes, T-Lymphocyte; D008074:Lipoproteins; D010455:Peptides; D014373:Tuberculin; D016753:Interleukin-10; C072681:Mycobacterium tuberculosis antigens; D011718:Pyrazinamide; D007371:Interferon-gamma; D004977:Ethambutol; D007538:Isoniazid; D012293:Rifampin