October 28, 2024, Immune Tolerance
First, we must establish a clear consensus. Namely, doctors are not deities, nor are they omnipotent. The interaction between a doctor and disease is akin to a martial arts duel. There are no absolute guarantees. Every doctor strives to do their utmost… Help! Help. All these matters concerning kidney transplantation. Each week, we discuss (and hope to popularize) a few related topics. Thank you for your careful attention to our content.
Successfully inducing immune tolerance in kidney transplantation and enabling patients to discontinue immunosuppressants is a shared dream of doctors and patients. It is also one of the most significant research priorities in the global transplantation field.
What Is Transplant Immune Tolerance?
Transplant immune tolerance is defined as the recipient’s immune system maintaining normal immune responses to other foreign antigens without the need for immunosuppressants.
CAR Treg Cells
Regulatory T cells (Tregs) play a crucial role in inducing and establishing immune tolerance following kidney transplantation. Studies have shown that pleiotropic Treg cells can prevent graft-versus-host disease following hematopoietic stem cell transplantation, but they are insufficient to prevent rejection after kidney transplantation. A recent study has found that donor-specific Treg cells can induce immune tolerance.
The researchers transduced a receptor, which recognizes the donor’s HLA antigen, onto the recipient’s natural regulatory T cells (nTregs), activating them into CAR Treg cells. This process did not alter the nTregs’ phenotype or genetic stability. However, compared to nTregs, CAR Treg cells demonstrated the ability to specifically target the donor with exceptionally strong immune hyporeactivity, completely preventing rejection. These cells may serve as a potential therapeutic target for donors and play a vital role in inducing and maintaining immune tolerance in kidney transplantation.
Zhongshan Hospital, affiliated with Fudan University, has conducted extensive research on immune tolerance in kidney transplantation. Building on the induction of immune tolerance in kidney transplantation in cynomolgus monkeys, kidney transplant recipients were pretreated with total lymphoid irradiation to modify their immune microenvironment. Significant clinical progress has been achieved using donor hematopoietic stem cell infusion combined with kidney transplantation to induce immune tolerance.
Among the 10 patients for whom this protocol has been implemented:
Some patients exhibit long-term donor-recipient chimerism in their peripheral blood and bone marrow, with chimerism rates reaching up to 50%.
In 2 cases, immunosuppressants were completely withdrawn, successfully eliminating dependency on them.
Four patients received only half the conventional dose.
We are continuing to optimize immune tolerance protocols to help more kidney transplant patients discontinue immunosuppressants.
We believe that CAR Treg cells will offer significant new insights for achieving immune tolerance in kidney transplantation.
