Peptide-Specific T Cell Response to Mycobacterium tuberculosis: Clinical Spectrum, Compartmentalization, and Effect of Chemotherapy

Abstract

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 pleu 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.

Author notes

Presented in part: 3rd International Conference on the Pathogenesis of Mycobacterial Infections, Stockholm, June 1996 (abstract O18).

Ethical approval for this study was given by the Harrow Local Research Ethical Committee (ref no. EC1646).

Financial support: Medical Research Council of the United Kingdom, Wellcome Trust, and European Union.

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Present affiliations: Department of Bacteriology, Veterinary Laboratory Agency, New Haw, Addlestone, Surrey, United Kingdom (H.M.V.); Division of Infectious Diseases, Case Western Reserve University, Cleveland, Ohio (K.A.W.); Department of Immunology, Division of Clinical Medical Sciences, King's College Hospital Medical School, Denmark Hill, London, United Kingdom (C.M.); Dept of Oral Medicine & Pathology, Guy's Hospital, London, United Kingdom (J.I.)