Impaired antigen-specific CD4(+) T lymphocyte responses in cavitary tuberculosis

Abstract

The clinical outcome in tuberculosis is determined by the host-pathogen interaction. Successful immune responses result in granulomas and curtailment of disease, whilst cavitation indicates a failing immune response. We sought to investigate the mechanisms involved in these processes. Fourteen patients with confirmed pulmonary tuberculosis underwent bronchoalveolar lavage with washings from areas of cavitation, or pulmonary infiltrates and also from the contra-lateral radiologically normal lung. Flow cytometry was utilised to determine both the leukocyte populations and the Mycobacterium antigen-specific T cell component of the response. Cavitation was associated with local neutrophilia and relative lymphopenia, whereas lymphocytosis and lower levels of granulocytes were detected from areas of pulmonary infiltrates and also from radiologically unaffected lobes. The Mycobacterium-specific T cell response from cavitary sites was significantly lower when compared to the radiologically normal lobes in the same individuals (p=0.003). By contrast, the Mycobacterium-specific T cell responses from areas of infiltrates were remarkably similar to paired responses from the radiologically unaffected lung (p=0.45). These results confirm the selective accumulation of Mycobacterium-specific lymphocytes in the lung in general though they also demonstrate that this is diminished in cavities. It remains unclear whether neutrophilia is a cause, or a result of cavitation in pulmonary tuberculosis.