Recruitment of antigen-specific Th1-like responses to the human lung following bronchoscopic segmental challenge with purified protein derivative of Mycobacterium tuberculosis

Abstract

Although the mechanisms of specific immunity to Mycobacterium tuberculosis in humans are poorly understood, responses of Th1-like CD4+ T cells appear to be essential for protection. We hypothesized that healthy individuals displaying positive skin-test responses to purified protein derivative of M. tuberculosis (PPD) would have the capacity to mobilize M. tuberculosis-specific Th1 cells to the lung in response to bronchoscopic challenge with PPD. Local instillation of 0.5 tuberculin units of PPD was followed 48 h subsequently by bronchoalveolar lavage (BAL) of PPD-challenged and control segments. In PPD-positive subjects, PPD challenge resulted in a 2.7-fold increase in total BAL cells and in an increase in the percentage of lymphocytes in BAL from 10 to 19%. The BAL lymphocytosis observed in PPD-challenged segments was characterized by an increased percentage of CD4+ T cells and by increased numbers of cells capable of antigen-specific interferon-gamma production. In contrast, PPD-negative subjects did not develop local inflammation following PPD challenge. These findings indicate that bronchoscopic challenge with PPD results in recruitment of antigen-specific recall responses to the lung. This novel approach may be useful in clarifying the basis of local immunity against M. tuberculosis, and could serve more generally as a model of the development of Th1-like responses in the human lung.