Functional differences and complementation between dendritic cells and macrophages in T-cell activation.

Abstract

Functional differences and cell collaboration between murine lymphoid dendritic cells (DC) and macrophages (M phi) in antigen presentation for T-cell activation were analysed with splenic DC and M phi, culture-derived bone-marrow (BM)-M phi, and DC-like and M phi-like cell lines. DC were the best stimulators of allogeneic mixed leucocyte reaction (MLR), but splenic M phi and small activated BM-M phi were almost as effective. In contrast to MLR stimulation, small activated BM-M phi were the most effective antigen-presenting cells (APC) for the presentation of whole Corynebacterium parvum (CP) organisms, possibly by virtue of their phagocytic and lysosomal functions, which could be particularly important for processing particulate antigens. Large activated BM-M phi were ineffective in stimulating MLR and CP-specific T-cell proliferation. The functional differences between BM-M phi subsets could not be explained by failure to express surface Ia or to take up antigen. Non-phagocytic APC, such as DC and the DC-like line P388AD.4, had low presenting activity for CP and were much less effective at presenting glutaraldehyde-fixed CP than M phi. This suggests that DC are dependent on the shedding of soluble antigen (reduced by glutaraldehyde fixation) from the bacteria, and they may also be less efficient than M phi at processing the fixed bacteria. The Ia- M phi-like line. P388D1, was devoid of APC activity, but could greatly enhance P388AD.4-induced T-cell proliferation to whole bacterial organisms. Similarly, co-culture of splenic DC and M phi produced very pronounced synergistic effects in proliferative responses to CP and keyhole limpet haemocyanin. The function of M phi n this partnership was sensitive to chloroquine and could not be replaced by M phi culture fluids or recombinant interleukin-1. Thus, M phi may contribute processed antigen in a form more suitable for presentation by DC. These results provide a rationale for the functional dichotomy between DC and M phi.