First Author | Hamano R | Year | 2014 |
Journal | Eur J Immunol | Volume | 44 |
Issue | 4 | Pages | 1005-15 |
PubMed ID | 24338997 | Mgi Jnum | J:209287 |
Mgi Id | MGI:5566925 | Doi | 10.1002/eji.201343434 |
Citation | Hamano R, et al. (2014) Ag and IL-2 immune complexes efficiently expand Ag-specific Treg cells that migrate in response to chemokines and reduce localized immune responses. Eur J Immunol 44(4):1005-15 |
abstractText | 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. |