• Richard F Silver, Lynn Zukowski, Susan Kotake, Qing Li, Fatima Pozuelo, Adriana Krywiak, and Rhonda Larkin.
• Division of Pulmonary and Critical Care Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4984. rfs4@po.cwru.edu
• Am. J. Respir. Cell Mol. Biol. 2003 Jul 1; 29 (1): 117-23.

AbstractAlthough 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.

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