ENHANCED PROLIFERATION OF CD4(-CELLS INDUCED BY DENDRITIC CELLS FOLLOWING ANTIGEN UPTAKE IN THE PRESENCE OF SPECIFIC ANTIBODY() T)

Afferent lymph dendritic cells bear an Fc gamma receptor which binds a ntigen/antibody complexes thereby enhancing uptake of antigen. In this report, we have addressed the question of whether the enhanced uptake of antigen results in augmented antigen presentation and T cell proli feration in in vitro secondary responses in sheep. Inclusion of affini ty-purified IgG anti-ovalbumin antibody in cultures of afferent lymph dendritic cells, purified CD4(+) T cells, and substimulating amounts o f ovalbumin resulted in a five- to 169-fold enhancement of T cell prol iferation. This effect was antigen-specific as replacement of the anti -ovalbumin antibody with an IgG anti-human serum albumin specific anti body did not cause enhanced T cell responses. The antigen-specific aug mentation required intact antibody Fc portions as F(ab')(2) fragments of the anti-ovalbumin antibodies were ineffective. The enhanced antige n presentation was found to be maximal with immune complexes in modera te antibody excess (three- to 30 fold), but still occurred at antibody /antigen ratios of 300. The augmented responses were inhibitable with anti-MHC Class II specific antibodies, indicating that at least some o f the antigen taken in via Fc gamma receptors entered a Class Il proce ssing pathway. The results thus show that antigen uptake via Fc gamma receptors on dendritic cells results in functional augmentation of ant igen presentation and T cell proliferation.