In Vivo Responses to Inhaled Proteins. III. Inhibition of Experimental Immune Complex Pneumonitis After Suppression of Peripheral Blood Lymphocytes

We have previously shown that inhaled Con A has a powerful enhancing effect on the formation of immune complexes between an inhaled antigen and circulating antibody. Immunohistochemical staining has demonstrated such complexes, together with host complement, in close association with foci of necrotizing destruction of the pulmonary parenchyma. We have postulated that Con A promotes immune complex formation indirectly through polyclonal activation of lymphocytes in the lung. In this paper we test this hypothesis in animals rendered unresponsive to Con A stimulation in vivo by i.v. administration of cholera toxin (CT). Such treatment raised the levels of cAMP in peripheral blood lymphocytes and inhibited their proliferative response to Con A in vitro. CT administration further blocked the local inflammatory response to intradermal injections of Con A, as well as the cell-mediated immune response to intradermal injections of BSA. Although CT failed to block the immune complex-mediated Arthus vasculitis in the skin, it did block production of immune complex pulmonary injury by antigen/mitogen aerosols, as did decomplementation with purified cobra venom factor. These findings support the hypothesis that polyclonal activation of pulmonary lymphocytes promotes immune complex-type alveolitis, possibly by facilitating interactions between humoral antibody and intra-alveolar antigen.