IL-10-mediated Induction of regulatory Foxp3+CD4+ T cells by F4/80+ macrophages in mixed allogeneic chimeras (102.12)

Abstract

Abstract Antigen-presenting cells including macrophages play a crucial role in shaping immune response to pathogens or allografts. The immune regulatory function of macrophages has not been fully understood. In the present study, the ability of donor F4/80+ splenic macrophages (SPMs) to induce recipient regulatory T cells (Treg) was studied using a B6-->Balb/c mixed chimeric mouse model, in which transplantation tolerance has been achieved. B6 F4/80+ SPMs in mixed chimeras induced significantly lower cell proliferation, more IL-10 and TGF-â products, and less IL-2 and IFN-ã products of recipient CD4+ T cells than B6 F4/80+ SPMs in non-chimeric B6 mice did, whereas they showed similar immunogenicity to the third part C3H CD4+ T cells. Importantly, donor B6 F4/80+ SPMs in mixed chimeras could induce recipient Foxp3+CD4+ Tregs from Foxp3-CD25-CD4+ T cells. Furthermore, donor B6 F4/80+ SPMs in mixed chimeras produced more IL-10 and less IFN-ã than those in non-chimeric mice when cultured with recipient Balb/c but not the third party CD4+ T cells. The induction of CD4+ Tregs by donor F4/80+ SPMs could be significantly blocked by anti-IL-10, but not TGF-â mAb. Therefore, donor F4/80+ SPMs may have the ability to induce recipient Foxp3+CD4+ Tregs partially via IL-10-dependent pathway. This study identified an additional mechanism for macrophages to induce and/or maintain transplant tolerance in mixed allogeneic chimeras.