HLA-G/APCs/regulatory cell known interactions, including DC-10. Tolerogenic mechanisms that are dependent on HLA-G–expressing monocytes or DC-10 and that may cooperate to create a tolerogenic milieu enriched in IL-10 and soluble HLA-Gs, and induce Tregs. (A) IL-10 present in the microenvironment promotes the up-regulation of membrane-bound HLA-G1 on APCs, including monocytes. (B) After a short interaction with HLA-G1–expressing APCs, CD4⁺ or CD8⁺ T cells (and NK cells, not shown) acquire HLA-G1–containing membrane fragments (trogocytosis) and become temporary Tregs. (C) Both soluble and membrane-bound HLA-G expression on APCs induces Tregs, some of which are characterized by a CD4^low and CD8^low phenotype. (D) In the presence of IL-10 secreted by DC-10, the interactions between ILT4 and HLA-G1 on DC-10, and HLA-G1 and ILT2 on T cells, respectively, promote the induction of Tr1 cells. (E) CD8⁺CD28⁻ T cells engage HLA class I on APCs and induce tolerogenic DCs, which overexpress ILT3 and ILT4.