After kidney transplantation, the medicine cannot be stopped Organ transplantation can indeed save lives, however, at the same time, the organ transplant recipient is also put on the golden hoop like the Monkey King being tamed, and the tight spell is “the need to take immunosuppressive drugs for life”. The body will have a spontaneous rejection of the “new foreigner”, as between strangers, it is difficult to meet like a brother, the relationship between the human body and the transplanted kidney also have to start from each other slowly acquaintance, mutual integration, during this period all unpleasant discomfort and small differences belong to the rejection reaction. No one likes to take medication. The thing about taking medication is that it adds to the financial burden, and according to statistics, the annual medical costs associated with it amount to tens of billions of dollars worldwide. The second is more troublesome and scary than the economic pressure – “immunosuppressive side effects”. Long-term use of immunosuppressants will lead to a general decrease in immunity after kidney transplantation, which may lead to a series of serious complications such as infection, cardiovascular disease, diabetes, malignancy and drug toxicity damage, thus affecting the long-term survival of the patient and the transplanted organ. Therefore, how to make the transplanted organs get along with the body while ensuring the health and safety of the post-transplant patients is the professional term “organ transplantation immune tolerance”, which allows the transplant patients to get rid of the lifelong use of immunosuppressive drugs. “It has always been a common dream of transplant doctors and patients, and one of the challenges that the international transplant field has been trying to overcome. Ensuring a safe and peaceful living environment for transplanted organs By “transplantation immune tolerance”, we mean that the immune system of the transplant recipient can distinguish between the enemy and the self without the use of immunosuppressants, for example, it will never attack the newly transplanted organ, but can immediately fight against any foreign invasion and kill all health-threatening destabilizing factors. The immune system of the transplant recipient is able to distinguish between the enemy and itself. Currently, the main strategies for immune tolerance induction include: (1) induction of central immune tolerance by clonal clearance of T cells in the thymus and B cells in the bone marrow; (2) induction of peripheral immune tolerance by blocking co-stimulatory signaling pathways, infusion or induction of regulatory immune cell production, and other methods to induce immune incompetence of T and B cells and suppress their proliferation or function. Since the induction of immune tolerance in organ transplantation involves a complex process of immune system modification and maintenance of immune regulation, relevant theoretical and clinical studies are still needed to develop safe and effective induction strategies. Exciting news: the dawn of clinical immune tolerance In recent years, Massachusetts General Hospital, Stanford University, Northwestern University and the Renal Transplantation Specialists of Zhongshan Hospital of Fudan University have conducted clinical studies on the induction of immune tolerance in more than 10 cases of hematopoietic stem cell infusion combined with kidney transplantation, respectively. The protocol began with whole lymphatic radiation pretreatment of kidney transplant recipients and simultaneous transfusion of donor hematopoietic stem cells. These clinical studies have been successful to varying degrees, with some patients having completely discontinued immunosuppression and significant reductions in treatment costs along with significant improvements in quality of life. It has been found that kidney transplant recipients have a long history of “donor-recipient chimerism” in their peripheral blood and bone marrow, where the recipient is immunologically unresponsive or hyporesponsive to the donor’s organ. In layman’s terms, this means that the recipient’s immune system is “modified” by infusing the donor’s hematopoietic stem cells into the recipient’s body so that it no longer sees the transplanted organ as a “foreign body” and no longer “attacks” it. The transplant recipient’s immune system is “modified” so that it no longer sees the transplanted organ as a “foreign body” and no longer “attacks” it. The renal transplantation specialty of Zhongshan Hospital of Fudan University believes that “donor hematopoietic stem cell infusion” may become a major breakthrough in the induction of immune tolerance in clinical renal transplantation. Possible mechanism of immune tolerance: remodeling of recipient’s lymphatic system by hematopoietic stem cells Possible mechanism of immune tolerance is the development, differentiation and evolution of donor’s hematopoietic stem cells through transfusion in the recipient’s body to educate each other and change the response pattern of the recipient’s immune system, ultimately producing specific immune tolerance. The specific mechanisms include: 1. The precursor cells of T and B cells generated from hematopoietic stem cells of the donor and recipient induce central tolerance in the central immune organs such as bone marrow and thymus of the recipient through immune recognition, clonal selection and rejection and formation of cell-in-cell structures; 2. The mature T and B cells from hematopoietic stem cells of the donor and recipient migrate from the central immune organs to the peripheral lymphoid tissues and induce formation of chimeric regulatory immune cells to achieve peripheral immune tolerance; 3. Donor hematopoietic stem cells or donor-educated recipient hematopoietic stem cells directly exercise the local immunosuppressive function of the transplanted kidney by secreting suppressive cytokines or microvesicles and other substances to promote peripheral immune tolerance. Hope for the future: promotion of hematopoietic stem cell-induced immune tolerance Clinical studies in the renal transplantation specialty of Zhongshan Hospital of Fudan University have achieved an important breakthrough in immune tolerance induction in some kidney transplantation patients, but the current overall success rate has not yet reached our expected goal, and there is still much room for improvement in improving the success rate of immune tolerance induction through optimized protocols. We believe that with the promotion of hematopoietic stem cell induction of immune tolerance, the rapid clinical dissemination and application of the new method will bring a better future for renal transplant patients.