In vitro cytotoxicity of CD8+ T cells in multi-drug-resistant tuberculosis. A preliminary report.
OBJECTIVE
Specific CD8+ T-cell cytotoxicity has been recognized as being involved in the elimination of drug-susceptible tuberculosis (DS-TB). Given that there is currently no information on the cytotoxic effector functions of CD8+ T cells in multi-drug-resistant tuberculosis (MDR-TB), our objective was to analyse the cytotoxic activity, both basal and stimulated, of CD8+ T cells from MDR-TB patients and compare it with that of DS-TB patients, as well as purified protein derivative (PPD)+ and PPD- subjects.


METHODS
Cytotoxic activity of CD8+ T cells from MDR-TB patients, DS-TB patients, PPD+ and PPD- subjects was measured by a colorimetric assay, using H37Rv culture filtrate protein as the antigenic stimulus.


RESULTS
Twenty-eight subjects were studied (7 MDR-TB patients, 7 DS-TB patients, 7 PPD+ subjects and 7 PPD- subjects). In the presence of the antigenic stimulus, the cytotoxic activity of CD8+ T cells from MDR-TB patients (% lysis) increased from 6.7% to 59.6% (P < 0.001). In DS-TB patients lysis increased from 3.2% to 22.5% (P < 0.001), whereas in PPD+ subjects it increased from 2.7% to 12.0% (P < 0.001) and in PPD- subjects from 1.3% to 3.2% (P < 0.001). Basal cytotoxic activity was significantly higher for MDR-TB patients than PPD+ and PPD- subjects (P = 0.003), but not compared with that for DS-TB patients (P = 0.05). Stimulated cytotoxic activity was highest for MDR-TB patients.


CONCLUSIONS
CD8+ T cells from MDR-TB patients showed an exaggerated cytotoxic activity after antigenic stimulation. Further studies are required to elucidate the role of this response in the immunopathogenesis of MDR-TB.
Sada-Ovalle
Isabel
I
Biochemistry Department, National Institute of Respiratory Diseases, Mexico DF, Mexico. i_sadamx@yahoo.com.mx
Torre-Bouscoulet
Luis
L
Valdez-Vázquez
Rafael
R
Lascurain
Ricardo
R
D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D016022:Case-Control Studies; D018929:Cell Culture Techniques; D003602:Cytotoxicity, Immunologic / Q000502:physiology*; D005260:Female; D006801:Humans; D006867:Hydrolases / Q000276:immunology; D008297:Male; D008875:Middle Aged; D014373:Tuberculin / Q000276:immunology; D018088:Tuberculosis, Multidrug-Resistant / Q000276:immunology* / Q000473:pathology*; D055815:Young Adult
D000942:Antigens, Bacterial; D014373:Tuberculin; D006867:Hydrolases; C527647:HsaD protein, Mycobacterium tuberculosis