Can Proliferation Signal Inhibitor-Induced Tregs Really Reflect Transplantation Tolerance in Clinical Solid Organ Transplantation?

Abstract

Exploring new immunosuppressive strategies inducing donor-specific hyporesponsiveness is a great challenge in transplantation. For this purpose, monitoring the alloimmune response is a critical step to carrying out protolerogenic immunosuppressive protocols. Regulatory T cells (Tregs), known as controlling various immune responses, were found to play an important part in allograft transplant tolerance. It is said that Rapamycin (RAPA), one of the proliferation signal inhibitors (PSIs), could achieve true tolerance through the induction of Tregs in clinical trials. Can PSI-induced Tregs in peripheral blood mononuclear cells (PBMC) really reflect transplantation tolerance in clinical solid organ transplantation?

Pretreatment of Rapamycin Before Allogenic Corneal Transplant Promotes Graft Survival Through Increasing CD4+CD25+Foxp3+ Regulatory T Cells

“…It has been reported that in vivo rapamycin administration contributed to selective activation and expansion of CD4 + CD25 + Foxp3 + Treg, not only in peripheral blood, but also, in secondary lymphoid organs and grafts, both of which merit graft survival. 15,[25][26] Therefore, it is reasonable to deduce that the increased numbers of CD4 + CD25 + Foxp3 + Treg found in draining lymph nodes and corneal grafts play a pivotal role in inhibiting graft rejection after allogenic keratoplasty. Moreover, previous research has observed that the number of Tregs increased shortly after rapamycin therapy was stopped, and then decreased gradually.…”

Spi6 Protects Alloreactive CD4+ But Not CD8+ Memory T Cell From Granzyme B Attack by Double-Negative T Regulatory Cell

“…The resistance of Tm cells to immune suppression might be inherent in their nature, as they are highly proliferative, with minimum requirements for antigen stimulation and co‐stimulatory activation . In addition, they are generally resistant to apoptosis .…”

“…In inbred rodent models, long‐term graft tolerance can be induced by various approaches including immunosuppressive drug treatment, preestablishment of mixed chimerism by bone marrow transplantation, T cell depletion, T cell signal blockade and induction of regulatory T cell (Tregs) . Notably, the manipulation of Tregs has been extensively shown as promising .…”