Inhibition of CD4+CD25+ regulatory T-cell function by calcineurin-dependent interleukin-2 production

Spleen tyrosine kinase (Syk) is a potent target for GvHD prevention at different cellular levels

“…22 Briefly, recipients were injected intravenously (i.v.) with 5 Â 10 6 wt BM cells after lethal irradiation with 900 cGy.…”

“…at the time of allo-HCT. 22 As a second model Burkitt luc cells were used. 24 Animals were injected either with A20 luc (BALB/c background, 2 Â 10 5 ) or with Burkitt luc (C57BL/6 background, 5 Â 10 4 ) i.v.…”

Calcineurin inhibitor-free GVHD prophylaxis with sirolimus, mycophenolate mofetil and ATG in Allo-SCT for leukemia patients with high relapse risk: an observational cohort study

“…It was also lower than in the earlier reported FLAMSA studies utilizing CYA, MMF and ATG as GVHD prophylaxis, and the reported incidence of grades II-IV acute GVHD was 49 and 28% without correction for the competing risk factor death. 1,2 Possibly by enhancing the numbers and function of CD4 þ CD25 þ regulatory T cells, 5 the combination of sirolimus and MMF seems to be a very efficient strategy for prophylaxis of acute GVHD and is at least as effective as CNI-based protocols. The 30% incidence of chronic GVHD is comparable with what we have seen in earlier studies 1,2 utilizing the FLAMSA preparative regimen (32-45%), but is much lower than in those studies (59-90%) that combined CNI and sirolimus.…”

“…As this process is IL-2-dependent, it is blocked by CNIs, but seems to be independent of inosine monophosphate dehydrogenase inhibition by mycophenolate mofetil (MMF). 5 Clinically, sirolimus has been proven to be effective as prophylaxis of allograft rejection in solid organ transplantation, 6,7 and in combination with CNI for GVHD prophylaxis after related and unrelated hematopoietic SCT, 8 as well as for therapy of acute 9 and chronic GVHD. [10][11][12] In addition to its immunosuppressive effects, sirolimus also has a potent antineoplastic activity.…”

Renal Transplantation in Patients with Sarcoidosis

“…Moreover, it has recently been shown that Treg may participate in the early stages of granuloma formation (43). Although CNI are likely to affect both Treg expansion and function both in vivo and in vitro (44), their ability to promote sarcoidosis recurrence is unlikely because all transplant recipients received CNI-based immunosuppresive regimen. Similarly, the role of induction therapy remains confusing because two patients with recurrence receive rabbit anti-thymocyte globulin and three IL-2 receptor antagonists.…”