Heterogeneity of macrophages and dendritic cells as accessory cells.

A number of different antigens was used to define the functional limits of Ia-bearing murine dendritic cells and macrophages in the processing and presentation of antigens for T cell activation. The results show considerable functional overlap as well as differences attributable to known properties of the cells. Thus both cell types could present soluble antigens up to the size of polymeric flagellin (M.W. in millions) about equally well. The nonphagocytic dendritic cells were most effective at inducing mixed leukocyte reactions in accordance with their high constitutive level of Ia expression. On the other hand, splenic macrophages were three to nine times better than dendritic cells at presenting particulate, heat-killed Corynebacterium parvum organisms to T cells lines, and small activated macrophages from bone marrow cultures were three times better again than splenic macrophages. Large activated bone marrow macrophages were not effective antigen presenters probably because of nonspecific suppression. These observations are consistent with the phagocytic and lysosomal activities of macrophages that enable them to ingest and process particulate antigen efficiently. Nevertheless, the capacity of dendritic cells and the dendritic-like line, P388.AD.4, to present particulate bacterial antigens suggests that these cells could either do the processing extracellularly or pick up soluble antigenic moieties shed from the bacteria and antigen processing macrophages. Glutaraldehyde fixation of C. parvum presumably stopped antigen shedding, since it produced a greater reduction of the T cell response with dendritic cells and P388.AD.4 as presenting cells than with macrophage presenters. Alternatively, the fixation could make the bacteria less "digestible" to dendritic cells than to macrophages. More characterization of the fate of antigens following encounter with accessory cells is necessary to distinguish between these possibilities.