Recruitment of Mycobacterium tuberculosis specific CD4+ T cells to the site of infection for diagnosis of active tuberculosis

Abstract

Accurate and early diagnosis of active tuberculosis (TB) is problematic as current diagnostic methods show low sensitivity (acid-fast bacilli smears), are time-consuming (culture of biological samples) or show variable results [Mycobacterium tuberculosis (MTB)-specific PCR]. In the course of infection, MTB-specific T cells clonally expand at the site of infection and may thus be used as diagnostic marker for active disease. In this cohort study, the frequency of MTB-specific, interferon (IFN)-gamma expressing CD4(+) T cells obtained from peripheral blood and the site of disease in 25 patients with suspected TB was assessed (n = 11, bronchoalveolar lavage; n = 7, pleural fluid; n = 1, ascites; n = 1, joint fluid; n = 5, cerebrospinal fluid). Amongst 15 patients who showed proven active TB infection, a striking increase of MTB-specific T cells was detected at the site of infection compared with peripheral blood (median increase: 28.5-fold, range: 7.25-531 fold; median of IFN-gamma-producing CD4(+) T cells from blood: 0.02%, range: 0-0.52%; median of IFN-gamma-producing CD4(+) T cells from the site of infection: 1.81%, range: 0.29-6.55%, P < 0.001). Recruitment of MTB-specific T cells to the site of infection yielded a sensitivity of 100% and specificity of 90%, irrespective of the compartment affected. The accumulation of MTB-specific T cells at the site of infection may prove as useful diagnostic marker for an accurate and rapid diagnosis of active TB.