Am. J. Respir. Cell Mol. Biol., Vol 10, No. 3, 03 1994, 339-346.
Alloantigen-induced immunoglobulin production in human lung: differential effects of accessory cell populations on IgG synthesis
DS Wilkes and JC Weissler
Department of Medicine, University of Texas Southwestern Medical Center, Dallas.
Local immunoglobulin production has been implicated in the pathogenesis of
lung allograft rejection. The role of varying classes of lung accessory
cells in stimulating an immunoglobulin (Ig) response in this setting as
well as cytokines necessary for Ig synthesis is unknown. The purpose of the
current study was to compare the accessory cell capabilities of lung
dendritic cells (DC), parenchymal macrophages (PM), and alveolar
macrophages (AM) in the generation of a humoral response to alloantigen.
Allogeneic AM induced a dose-dependent production of IgG from peripheral
blood mononuclear cells. In contrast, allogeneic DC and PM were unable to
induce IgG synthesis. The inability of DC to stimulate IgG synthesis was
observed despite a potent induction of T-cell proliferation and
interferon-gamma (IFN-gamma) production. Additionally, supernatants from DC
cultures suppressed AM- induced IgG production, suggesting that a soluble
inhibitor of IgG synthesis was produced by DC-stimulated lymphocytes.
AM-induced IgG synthesis was predominantly the result of IgG1 and IgG2
production. Experiments with blocking antibodies to either IFN-gamma or
interleukin- 4 (IL-4) revealed that both IFN-gamma and IL-4 participated in
IgG synthesis, while only IFN-gamma was required for IgG2 production. These
data demonstrate a discordance between the ability of lung accessory cells
to induce T-cell proliferation and IgG synthesis. Furthermore, these
findings suggest that local induction of either IL-4 or IFN-gamma is
involved in stimulation of an IgG response to lung alloantigen.
