ASP1126, a Novel Sphingosine-1-Phosphate–Selective Agonist With a Favorable Safety Profile, Prolongs Allograft Survival in Rats and Nonhuman Primates in Combination With Tacrolimus With a Broad Safety Margin for Bradycardia

The Entangled World of Memory T Cells and Implications in Transplantation

“…Of note, FTY720 combined with CTLA4-Ig or tacrolimus significantly increased graft survival, primarily by decreasing the frequency of T CM and T EM in the periphery and delaying overall T-cell recruitment into the graft in both presensitized mouse models and NHPs, which suggests it could function to regulate the alloreactive memory T-cell response even when administered only as a shortcourse therapy after transplantation. 74,75 FcγRIIB is an inhibitory Fc receptor expressed on a subset of CD8 + memory T cells. 76,77 It was observed that an increase in FcγRIIB + CD8 + memory T cells was associated with decreased risk of allograft rejection, and its deletion on alloreactive memory cells led to increased production of proinflammatory cytokines and increased rejection.…”

“…Of note, FTY720 combined with CTLA4-Ig or tacrolimus significantly increased graft survival, primarily by decreasing the frequency of T CM and T EM in the periphery and delaying overall T-cell recruitment into the graft in both presensitized mouse models and NHPs, which suggests it could function to regulate the alloreactive memory T-cell response even when administered only as a short-course therapy after transplantation. 74,75…”