Enhanced proliferation of CD4(+) T cells induced by dendritic cells following antigen uptake in the presence of specific antibody

Afferent lymph dendritic cells bear an Fc gamma receptor which binds antigen/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 proliferation in in vitro secondary responses in sheep. Inclusion of affinity-purified IgG anti-ovalbumin antibody in cultures of afferent lymph dendritic cells, purified CD4(+) T cells, and substimulating amounts of ovalbumin resulted in a five- to 169-fold enhancement of T cell proliferation. This effect was antigen-specific as replacement of the anti-ovalbumin antibody with an IgG anti-human serum albumin specific antibody did not cause enhanced T cell responses. The antigen-specific augmentation required intact antibody Fc portions as F(ab')(2) fragments of the anti-ovalbumin antibodies were ineffective. The enhanced antigen presentation was found to be maximal with immune complexes in moderate 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 of the antigen taken in via Fc gamma receptors entered a Class Il processing pathway. The results thus show that antigen uptake via Fc gamma receptors on dendritic cells results in functional augmentation of antigen presentation and T cell proliferation.