Indirect inhibition of in vivo and in vitro T-cell responses by intravenous immunoglobulins due to impaired antigen presentation.
Several clinical studies done with intravenous immunoglobulin (IVIg)-treated autoimmune patients as well as several in vitro studies have revealed that IVIg can reduce polyclonal T-cell activation and modify their cytokine secretion pattern. However, their effect on (auto)antigen-specific T-cell responses has never been addressed directly. In the present work, we used an in vivo model of induction of antigen-specific T-cell responses and an in vitro antigen presentation system to study the effects of IVIg on T-cell responses. The results obtained showed that IVIg inhibited both the in vivo and in vitro antigen-specific T-cell responses but that this effect was the indirect consequence of a reduction in the antigen presentation ability of antigen-presenting cells. The inhibitory effect of IVIg was FcgammaRIIb-independent, suggesting that IVIg must interfere with activating FcgammaRs expressed on antigen-presenting cells to reduce their ability to present antigens. Such inhibition of T-cell responses by reducing antigen presentation may therefore contribute to the well-known anti-inflammatory effects of IVIg in autoimmune diseases.
Aubin
Eric
E
Department of Research and Development, Héma-Québec, Québec City, Canada.
Lemieux
Réal
R
Bazin
Renée
R
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation; D000936:Antigen-Antibody Complex / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D001667:Binding, Competitive; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage*; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D017452:Receptors, IgG / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
D000936:Antigen-Antibody Complex; C408982:CPG-oligonucleotide; C499172:Fcgr2b protein, mouse; D016756:Immunoglobulins, Intravenous; D009838:Oligodeoxyribonucleotides; D017452:Receptors, IgG; D010047:Ovalbumin