Human Alveolar Macrophage Support of Lymphocyte Responses to Mitogens and Antigens

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Abstract
Observations from animal studies and investigations using human peripheral-blood-derived macrophages may not be representative of human alveolar macrophage functions. Thus, we extensively examined and compared accessory cell functions of autologous human alveolar macrophages and peripheral-blood-derived monocytes and macrophages obtained from healthy, nonsmoking volunteer subjects. The alveolar and peripheral-blood-derived cells differed in ability to enhance mitogen- and antigen-stimulated transformation responses of purified autologous lymphocytes. Peripheral-blood-derived cells supported greater lymphocyte responses to optimal concentrations of several mitogens, but alveolar macrophages supported much greater responses to suboptimal concentrations of the mitogen phytohemagglutinin. Peripheral-blood-derived macrophages supported, but alveolar macrophages did not support, lymphocyte responses to streptococcal and influenza virus antigens. Such relative accessory cell functions of the different macrophages and monocytes were not due to different kinetics of response, nor were they due to differences in the proportion of macrophages required to support the lymphocyte responses. These data indicate that human alveolar macrophages have functional characteristics different from autologous peripheral-blood-derived monocytes and macrophages. Such differences may be important in both pulmonary immune homeostasis and in the pathogenesis of pulmonary disease.