This article discusses newer cellular immunological and immunoregulatory events operative in the pathogenesis of "allergic alveolitis" (aa). An early increase in neutrophils and
chemotactic factors followed by an influx of macrophages and lymphoid cells with ultimate production of
granulomas have been demonstrated in the bronchoalveolar lavage (BAL) fluids of experimental animals and of man in aa. Transfer of specifically sensitized lymph node and spleen cells intraperitoneally followed by
antigen challenge via the respiratory tract route has resulted in production of pulmonary lesions closely resembling those observed in human aa in several animal species. Activated alveolar macrophages and T-cells, local lymphokine production, and elevated
immunoglobulin levels in BAL fluid have also been demonstrated repeatedly in experimental animal models of these diseases. High levels of
interleukin-1 have also been demonstrated in aqueous extracts prepared from pulmonary granulomatous lesions. Other studies have indicated a role for macrophage-derived
lipoxygenase products in production of experimental pulmonary granulomatous
inflammation. Mononuclear cell pulmonary infiltrates have been inhibited by
corticosteroids, the use of antimacrophage serum, neonatal
thymectomy, cobra factor
venom, and
cyclosporin. A T suppressor factor and other suppressor factors from adherent cell populations have also been shown to dampen or modulate experimental
granuloma formation. Appropriately sensitized animals which demonstrate chronic pulmonary granulomatous
inflammation can also become "desensitized" following a series of
antigen challenges. The desensitization produced is immunospecific and nontransferable with immune serum. Studies of bronchoalveolar lavage fluids in man have demonstrated a very high percentage of lymphocytes in BAL fluids. The percentage of suppressor cytotoxic T-cells is usually above 40% and CD4:CD8 ratios are reversed. Evidence also suggests that suppressor lymphocytic alveolitis is a chronic event in patients with aa. Immunogenetic studies of granulomatous
pneumonitis resembling aa in different strains of mice have shown that certain high-responder strains develop intense
granulomas after inoculation with killed bacille Calmette-Guérin (BCG), whereas other low-responder strains do not. The intensity of the pulmonary
granuloma formation in this model has been shown to be a dominant and polygenic trait and to be linked to the
immunoglobulin heavy chain locus (IgH). Strains that develop intense, chronic granulomatous
inflammation have usually proved to be anergic, and the anergy also appears to be under genetic control.(ABSTRACT TRUNCATED AT 400 WORDS)