Abstract
Immune tolerance against alloantigens plays an important role in the success of clinical organ and allogeneic hematopoietic stem cell transplantation. The mechanisms of immune tolerance to alloantigens have gradually been elucidated over time. Although there have been numerous reports to date on the induction of tolerance to alloantigens, the establishment of mixed chimerism is well-known to be crucial in the induction and maintenance of immune tolerance for either of the methods. Since the early 1980s, the murine system of cyclophosphamide (Cy)-induced tolerance has also been examined extensively. The present review focuses on studies conducted on Cy-induced immune tolerance. Clinical data of patients with allogeneic transplantation suggest that the posttransplant Cy method to induce immune tolerance has been successfully translated from basic studies into clinical practice.
Highlights
Donor availability remains a limiting factor for success of allogeneic hematopoietic stem cell transplantation
The “cellsfollowed-by-Cy system” in combination with using anti-T-cell monoclonal antibody and low-dose total body irradiation (TBI) on day −1 could induce a profound tolerance with sustained mixed chimerism to skin or other solid organs in various mouse combinations with differing major histocompatibility complex (MHC) and minor antigens [5, 27,28,29] (Figure 1B)
Intrathymic Mixed Chimerism in the Maintenance Phase In AKR/J→C3H/He combinations, while Thy-1.1-positive T cells from donor AKR/J were observed in peripheral lymph nodes beginning immediately after the induction of tolerance, Thy-1.1positive T cells from the donor AKR/J were not observed in the thymus of recipient C3H/He on day 14 after Cy administration, and Vβ6-positive T cells reactive to donor Mlsa antigens were found at normal levels [32]
Summary
Donor availability remains a limiting factor for success of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Opportunistic infections which are associated with the suppression of cell-mediated immunity have become pressing issues related to kidney transplantation, the advances in immunosuppressants such as cyclosporine and tacrolimus have resulted in decreasing incidence of graft rejection in organ transplantation [3]. These are as a result of non-specific immunosuppression, which suppresses the function of T cells in general. Cyclophosphamide-Induced Tolerance through the recipient-specific induction of immune tolerance against donor graft is the eventual goal for success of these allogeneic transplantation This can be approached by selectively depleting alloreactive T cells; there is still no established method to achieve this goal. We will provide a general outline of this topic, including a history of the basic research conducted to date
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