EVIDENCE FOR A TH1-LIKE BRONCHOALVEOLAR T-CELL SUBSET AND PREDOMINANCE OF INTERFERON-GAMMA GENE ACTIVATION IN PULMONARY TUBERCULOSIS

Mycobacterium-specific human helper T-cell clones produce a Th1 pattern of cytokines in vitro: interferon-gamma (IFN-gamma) and interleukin-2 (IL-2), but little or no IL-4 or IL-5. To test the hypothesis that a similar Th1-like pattern of cytokine gene expression occurs in vivo in pulmonary tuberculosis we used in situ hybridization to detect cytokine mRNA expression by bronchoalveolar lavage cells from nine patients with microbiologically confirmed tuberculosis and nine control subjects. Because IFN-gamma may also originate from alveolar macrophages, simultaneous immunocytochemistry and in situ hybridization was applied to determine whether cytokine mRNA was localized to bronchoalveolar macrophages in addition to T-lymphocytes. When samples from patients with tuberculosis and control subjects were compared, there was a significant increase in numbers of IFN-gamma mRNA-positive BAL cells per 1,000 among patients with tuberculosis (p < 0.01). Differences between the two groups in the proportions of cells expressing IL-2, IL-4, or IL-5 mRNA were not significant. Expression of IFN-gamma mRNA by macrophages was detected (median, 14.3% of IFN-gamma mRNA-positive BAL cells). However, the majority of IFN-gamma mRNA expressing BAL cells were T-lymphocytes (median, 80.7%). Activation of Th1-like bronchoalveolar T-lymphocytes, together with production of IFN-gamma by alveolar macrophages, may contribute to the local cellular immune response in pulmonary tuberculosis.