Ag and IL-2 immune complexes efficiently expand Ag-specific Treg cells that migrate in response to chemokines and reduce localized immune responses

European Journal of Immunology
Ryoko HamanoNaofumi Mukaida

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 reduc...Continue Reading

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Citations

Aug 28, 2020·Frontiers in Immunology·Tiantian GuoZhengfei Zhu
Jul 22, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Asmaa El BeidaqRudolf A Manz
Dec 29, 2020·Frontiers in Immunology·Christopher W M LinkRudolf A Manz
Dec 15, 2020·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Kento KawaiFadi Issa

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