Tolerogenic Dendritic Cells on Transplantation: Immunotherapy Based on Second Signal Blockage

Figure 2

Mechanism of action of CTLA4-Ig on DC. CTLA4-Ig soluble molecule binds to B7 (CD80/CD86) molecules on DC. CTLA4 presents a higher affinity to B7 molecule and competes with CD28 for this ligation. This interaction induces downregulation of B7 gene transcription and upregulation of IDO as well as secretion of sHLA-G. sHLA-G can stimulate Th2 and inhibit Th1 profile. DC: dendritic cell; CTLA4-Ig: extracellular domain of human CTLA4 with a portion of the Fc region of IgG; IDO: indoleamine 2,3-dioxygenase; sHLA-G: soluble HLA-G; Th: T helper; IL: interleukin; IFN: interferon; TNF: tumor necrosis factor.