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Polarized Type 1 Cytokine Profile in Bronchoalveolar Lavage T Cells of Patients with Hypersensitivity Pneumonitis¹

Hisato Yamasaki^2,*, Masayuki Ando^*, William Brazer, David M. Center and William W. Cruikshank

^* First Department of Internal Medicine, Kumamoto University School of Medicine, Kumamoto, Japan; and Pulmonary Center, Boston University School of Medicine, Boston, MA 02118

Hypersensitivity pneumonitis (HP) is characterized by an inflammatory lymphocytic alveolitis comprised of both CD8⁺ and CD4⁺ T cells. Animal models suggest that HP is facilitated by overproduction of IFN-, and that IL-10 ameliorates severity of the disease, indicating a Th1-type response. To determine whether a Th1 phenotype in HP also exists clinically, bronchoalveolar lavage (BAL) and peripheral blood (PB) T cells were obtained from HP individuals and analyzed for Th1 vs Th2 cytokine profiles. It was determined that soluble OKT3-stimulated BAL T cells cocultured with alveolar macrophages produced more IFN- and less IL-10 than PB T cells cocultured with monocytes, but no difference was observed in IL-4 production. The monocytic cells did not account for this difference, as CD80 and CD86 expressions were similar, and coculturing PB T cells with alveolar macrophages resulted in no difference in IFN- production. Similarly, there was no difference in IL-12 production between stimulated BAL or PB T cells; however, addition of rIL-12 significantly increased production of IFN- by BAL T cells, but not by PB T cells. This effect was due to a difference in IL-12R expression. High affinity IL-12R were only present in association with BAL T cells. These studies indicate that clinical HP is characterized by a predominance of IFN--producing T cells, perhaps resulting from a reduction in IL-10 production and an increase in high affinity IL-12R compared with blood T cells.

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