INTRAPULMONARY ANTIGEN DEPOSITION IN THE HUMAN LUNG - LOCAL RESPONSES

We hypothesized that, as in animal models, localized deposition of ant igen into the human lung would induce local inflammatory and immune re sponses in antigen-exposed sites. To test this hypothesis, segmental i nstillation of a well-characterized, highly immunogenic, soluble antig en, keyhole limpet hemocyanin (KLH) was performed in 10 healthy, nonsm oking volunteers. Ten to fifteen days after instillation, bronchoalveo lar lavage (BAL) was performed in immunized segments (IS) and contrala teral control segments (CS) and local responses to antigen instillatio n were assessed by comparing IS and CS BAL. Greater albumin concentrat ions and cell recoveries were found in IS than in CS BAL, suggesting l ocal inflammation. Although total numbers of each cell type were incre ased, relative proportions of alveolar macrophages, lymphocytes, and n eutrophils were similar in IS and CS BAL. CD4/CD8 ratios in IS BAL sam ples were greater than those in CS samples, because of higher numbers of CD4(+) lymphocytes in IS than in CS BAL but similar numbers of CD8( +) lymphocytes. Anti-KLH IgG and IgA concentrations were greater in IS than in CS BAL. However, anti-KLH IgG/albumin ratios were similar in IS BAL and serum, suggesting that anti-KLH IgG had reached IS by passi ve transudation from the circulation. In contrast, anti-KLH IgA/albumi n concentrations were greater in IS BAL than in serum, suggesting loca l production, and/or active transport of serum-derived anti-KLH IgA in to the IS. Fractionation of serum and IS BAL on sucrose gradients demo nstrated that anti-KLH IgA activity was largely associated with 11S po lymeric IgA in both locations. These studies demonstrate that segmenta l instillation of soluble KLH into the human lung results in local inf lammation, a local lymphocytic response characterized by disproportion ate accumulation of CD4(+) T cells and a local specific antibody respo nse characterized by disproportionate accumulation of polymeric IgA. T he results suggest important roles for CD4(+) T cells and secretory Ig A in respiratory tract responses to exogenous soluble antigen.