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 II 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.
Coughlan
S
S
Department of Veterinary Pathology, University of Edinburgh, Summerhall, UK.
Harkiss
G D
GD
Hopkins
J
J
D000818:Animals; D000918:Antibody Specificity; D017951:Antigen Presentation; D000941:Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D007074:Immunoglobulin G / Q000494:pharmacology; D066298:In Vitro Techniques; D008196:Lymph / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D010047:Ovalbumin / Q000276:immunology / Q000493:pharmacokinetics; D017452:Receptors, IgG / Q000378:metabolism; D012756:Sheep / Q000276:immunology*
D000941:Antigens; D007074:Immunoglobulin G; D017452:Receptors, IgG; D010047:Ovalbumin