EFFECT OF HUMAN LUNG ALLOGRAFT ALVEOLAR MACROPHAGES ON IGG PRODUCTION - IMMUNOREGULATORY ROLE OF INTERLEUKIN-10, TRANSFORMING GROWTH-FACTOR-BETA, AND INTERLEUKIN-6

Alveolar macrophages (AM) are crucial to initiating and maintaining local immune responses. The increased susceptibility to pulmonary infections in lung allograft recipients may be due to impaired AM function resulting in diminished cellular and humoral immunity, We have previously reported that control AM were potent stimulators of IgG production from allogeneic peripheral blood mononuclear cells (PBM) in a manner that was dependent on gamma-interferon (gamma IFN), The ability of allograft AM to induce IgG production is unknown, The purpose of the current study was to compare the ability of allograft and control AM to induce IgG production from allogeneic PBM. In contrast to control AM which induced a dose-dependent stimulation of IgG production from allogeneic PBM, allograft AM were highly suppressive of IgG production. The inhibition was not due to a lack of allograft AM stimulation of gamma IFN production from responding lymphocytes. Supernatants from allograft AM were highly suppressive of control AM-induced IgG production. Allograft AM produced greater quantities of interleukin (IL-10) than control AM while transforming growth factor-beta (TGF-beta) production from these cells was comparable. Blocking antibodies to IL-10 and TGF-beta reversed the inhibition of IgG production to 63% and 60% of control, respectively. In addition, the production of interleukin 6 (IL-6), a macrophage-derived cytokine crucial to the stimulation of IgG synthesis, was deficient in the allograft AM. Addition of IL-6 to allograft AM and allogeneic PBM co-cultures restored IgG synthesis. These data suggest that impaired IL-6 production in combination with IL-10 and TGF-beta synthesis by allograft AM may prevent adequate IgG responses to pathogens in vivo.