**5. Conclusion**

nor's bone marrow hematopoietic cells, a condition referred to as full chimerism [57]. Experimental data have confirmed that the infusion of donor-derived bone marrow cells can prolong allograft survival by still incompletely understood mechanisms [58]. Howev‐ er, the translation of this model from animals to humans has remained a very challeng‐ ing task. In particular, an immunosuppression-free state has been achieved only sporadically after living-related donor renal transplantation, whereas similar findings have never been documented after deceased donor renal transplantation [57,59–63]. In some studies, the perioperative infusion of donor bone marrow seems to reduce the inci‐ dence of acute and chronic rejection, [57,60,61] and to improve graft function when in‐

Total lymphoid irradiation was originally developed as a nonmyeloablative treatment for Hodgkin disease [64]. This treatment modality was first used about 40 years ago to in‐ duce prolonged renal allograft survival. However, total lymphoid irradiation has signifi‐ cant short- and long-term effects on lymphocyte subpopulations through suppression of activated T cells and the IL-2 pathway. Importantly, as the doses of radiation required for total lymphoid irradiation to be effective are high, with 10 doses of total lymphoid ir‐ radiation (80 to 120 cGy) targeted to the lymph nodes, spleen, and thymus, [54] its clini‐ cal application is limited by the toxicity that occurs with such high doses. With the advent of more effective immunosuppressive drugs and cytolytic therapy with antithy‐ mocyte globulin and monoclonal antibodies, the use of total lymphoid irradiation has de‐ clined considerably and is mainly applied, as stated earlier, as a nonmyeloablative preparative regimen of total lymphoid irradiation in combination with the infusion of do‐

nor-derived cells to induce a state of lymphohematopoietic chimerism [65-71].

living kidney transplantation is being performed [72–76].

Currently, Japan has a serious shortage of cadaveric organs. As a result ABO incompatible

Between 2001 and 2004, the ABO-incompatible living kidney transplantation procedure used a 1-week pretransplant immunosuppression with tacrolimus/mycophenolate mofetil/methyl‐ prednisolon. During this period, splenectomy was performed in all cases and the short–term outcome was excellent [77]. Graft survival was 93.5% at three years and 91.3% at five years in

The spleen is involved in the production of B lymphocytes and IgM, so splenectomy can result in decreased antibody content and increased tolerance [79]. This effect could be considered analogous to the effect of rituximab (anti-CD20+ monoclonal antibody), [80,81] which prevents acute rejection mediated by antibodies, resulting in a tolerogenic effect. Conversely, recent studies show the important role of the spleen for the induction and maintenance of regulatory CD4+CD25+ T cells, which are important for self-tolerance [82,83]. This immune regulatory mechanism is known as non-specific suppression of acti‐

fused not only systemically but also intrathymically [62,63].

*4.1.3. Total lymphoid irradiation protocols*

472 Current Issues and Future Direction in Kidney Transplantation

**4.2. Surgical procedures**

these patients [78].

Despite advances in understanding the cellular and molecular mechanisms of the alloimmune response, tolerance induction in renal transplantation remains an important clinical challenge. In clinical practice, prevention of graft rejections has combined tolerance mechanisms, such as suppression of activated T cells, inhibition the IL-2 pathway, decreased antibody production, and t chimerism. However, no completely satisfactory results have been achieved. The reason for these seemingly insurmountable challenges stems from the properties of the alloimmune response, which are not yet completely understood.
