Altered immunosuppressive activity of alveolar macrophages in farmer's lung disease

Since normal alveolar macrophages (AMs) can suppress T-cell proliferation to mitogenic and antigenic stimuli both in vitro and in vivo, we questioned whether an altered AM immunosuppressive activity could account for the alveolar lymphocytosis observed in farmer's lung (FL) and whether granulocyte/macrophage colony-stimulating factor (GM-CSF), a cytokine able to abrogate AM-induced immunosuppression, is involved in the process. The ability of different concentrations of AMs to inhibit lymphocyte proliferation in response to the T-cell-specific mitogen phytohaemagglutin (PHA) after in vitro culture was tested in three groups of subjects: 12 patients with FL; four asymptomatic farmers (AS); and six normal volunteers (N). Release of GM-CSF by AMs was also measured. At all ratios tested, AMs from patients with FL did not suppress the lymphoproliferation but instead had an enhancing effect. In AS, AMs enhanced the proliferation at a lower ratio but inhibited it at high ratios. In N subjects, as described previously, AMs increasingly inhibited the blastogenesis of lymphocytes (L) at increasing ratios of AM:L. In some patients with FL, AMs spontaneously released more GM-CSF than in normal volunteers (206 +/- 84 versus 29 +/- 14 pg.mL-1, respectively). In AS, GM-CSF release was intermediate (74 +/- 36 pg.mL-1). In conclusion, a defect in the ability of alveolar macrophages to suppress the proliferation of lymphocytes in the lung of patients with farmer's lung is a major factor accounting for the development of the observed lymphocytic alveolitis. Granulocyte/macrophage colony-stimulating factor could be one factor which may contribute to this alteration.