CELLULAR IMMUNOREGULATION OF ACUTE PULMONARY INFLAMMATION IN STRAIN 2 AND STRAIN 13 GUINEA PIGS

The participation of cell-mediated mechanisms in the immunoregulation of acute pulmonary inflammation was investigated in strain 2 and strain 13 guinea pigs. These two strains differ only with respect to those genes which control immune responsiveness. The acute inflammatory response, elicited in the guinea pig lung by a protocol of immunization and aerosol challenge with ovalbumin, was evaluated at 12, 24, 48, 72 and 96 hours postchallenge. Both strains manifest a characteristic influx of inflammatory cells into the lungs as well as pulmonary edema and hemorrhage. Inflammatory injury, as assessed by histological evaluation, cell recovery from the lung and the proportion of macrophages in the bronchoalveolar lavage cell population, is maximal at 24 hours postchallenge in both strains, and is still evident at 96 hours postchallenge in strain 2 guinea pigs. Acute inflammation is of shorter duration in the lungs of strain 13 guinea pigs. A role for cellular immune responses to inhaled antigen was suggested by the antigen-specific blastogenesis of bronchoalveolar lavage T lymphocytes. Strain 2 bronchoalveolar lavage T cells exhibited a biphasic proliferative response to ovalbumin that was not observed in peripheral blood. The decreased blastogenic response to ovalbumin at 72 hours postchallenge was associated with functional activity of an antigen-specific suppressor T lymphocyte recovered from the lung at this postchallenge time. This suppressor cell population was shortlived in vitro, histamine type II receptor-positive, Ia antigen-positive, and could be induced by preincubation in the presence of antigen. In contrast, ovalbumin-induced blastogenesis of strain 13 guinea pig bronchoalveolar lavage T cells was significantly (p \u3c 0.05) elevated only at 72 hours postchallenge, coincident with the resolution of disease. A suppressor T lymphocyte could be recovered from the strain 13 lung at 24 through 96 hours postchallenge, and activation of a cellular histamine type II receptor was not critical for expression of function. Peripheral blood and bronchoalveolar cell proliferative responses to antigen and mitogen were more closely parallel in strain 13 guinea pigs. Alveolar macrophages may interact with other cellular immune reactants present in the lung, thereby assuming a central role in the mediation of inflammation. The increased expression of Ia antigens by strain 2 alveolar macrophages throughout the course of disease may facilitate antigen presentation, contributing to maintenance of the inflammatory state. Alternatively, prostaglandin production by alveolar macrophages may be partially responsible for resolution of disease. (Abstract shortened with permission of author.