title: Ag and IL-2 immune complexes efficiently expand Ag-specific Treg cells that migrate in response to chemokines and reduce localized immune responses.
abstract: An intravenous administration of a high-dose antigen (Ag) can induce immune tolerance and suppress the immune response, but the mechanism remains unclear. We recently proved that a combined i.v. administration of OVA and IL-2-anti-IL-2 Ab immune complexes (IL-2 ICs) efficiently expands OVA-specific Treg cells in the thymus and induces their migration into peripheral blood, by using OVA-specific TCR Tg-expressing DO11.10 mice. Here, we demonstrate that the expanded OVA-specific Treg cells rapidly move into the air pouch after OVA injection in DO11.10 mice. The migration was inhibited by blocking the axis of a chemokine receptor, CCR2. Moreover, prior treatment with OVA and IL-2 ICs enhanced OVA-specific Treg-cell migration and inhibited OVA-induced delayed-type hypersensitivity (DTH) reactions in the skin of BM chimeric mice with 15% of T cells expressing OVA-specific TCR. Blocking the CCR2 axis reversed this suppression of DTH in these mice. Furthermore, prior treatment with OVA and IL-2 ICs effectively reduced DTH reactions even in WT mice possessing only a very small population of OVA-specific T cells. Thus, the treatment with Ag and IL-2 ICs can efficiently expand Ag-specific Treg cells with the capacity to migrate and reduce localized immune responses.
authors: Division of Rheumatology, Department of Internal Medicine, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan.
authors: Ryoko
authors: R
authors: Hamano
authors: Tomohisa
authors: T
authors: Baba
authors: Soichiro
authors: S
authors: Sasaki
authors: Utano
authors: U
authors: Tomaru
authors: Akihiro
authors: A
authors: Ishizu
authors: Mitsuhiro
authors: M
authors: Kawano
authors: Masakazu
authors: M
authors: Yamagishi
authors: Naofumi
authors: N
authors: Mukaida
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D000936:Antigen-Antibody Complex / Q000008:administration & dosage / Q000276:immunology*; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D018925:Chemokines / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000517:prevention & control; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology*; D054390:Receptors, CCR2 / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D000936:Antigen-Antibody Complex; C515335:Ccr2 protein, mouse; D018925:Chemokines; D007376:Interleukin-2; D054390:Receptors, CCR2; D010047:Ovalbumin
keywords: Antigen (Ag); CCR2; IL-2; Treg cells; thymus