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

Context. 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]. Objectives. 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. Design. In this cohort study, the frequency of MTB‐specific, interferon (IFN)‐γ 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). Results. 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‐γ‐producing CD4⁺ T cells from blood: 0.02%, range: 0–0.52%; median of IFN‐γ‐producing CD4⁺ T cells from the site of infection: 1.81%, range: 0.29–6.55%, P < 0.001). Main outcome measure. 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. Conclusions. 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.