The numbers of organ and tissue grafts performed in the United States in 2014 are shown. HSC, hematopoietic stem cells (includes bone marrow, peripheral blood HSCs, and cord blood transplants). *Number of grafts includes multiple organ grafts (for example, kidney and pancreas, or heart and lung). For solid organs, 5‑year survival of the transplanted graft is based on transplants performed between 2002 and 2007. Data from the United Network for Organ Sharing. #Kidney survival listed (81.4%) is for kidneys from living donors; 5‑year survival for cadaveric donor transplants is 69.1%. †Pancreas survival listed (53.4%) is when transplanted alone; 5‑year survival when transplanted with a kidney is 73.5%. ** Includes autologous and allogeneic transplants. ‡Successful HSC engraftment is assessed within weeks of transplant, not years. Nearly all solid organ grafts (e.g., kidney, heart) require long‑term immunosuppression.
15-36 The converse of graft rejection is graft-versus-host disease.
Transplantation of hematopoietic stem cells (HSCs) from peripheral blood, bone marrow, or fetal cord blood is a successful therapy for some tumors derived from hematopoietic cells, such as certain leukemias and lymphomas. By replacing genetically defective stem cells with normal donor ones, HSC transplantation can also be used to cure some primary immunodeficiencies (see Chapter 13) and other inherited blood cell disorders, such as severe forms of thalassemia. In leukemia therapy, the recipient’s bone marrow, the source of the leukemia, must first be destroyed by a combination of irradiation and aggressive cytotoxic chemotherapy.
One of the major complications of allogeneic HSC transplantation is graftversus-host disease (GVHD), in which mature donor T cells present in preparations of HSCs recognize the tissues of the recipient as foreign, causing a severe inflammatory disease in multiple tissues, but particularly involving the skin, intestines, and liver and characterized by rashes, diarrhea, and liver dysfunction (Fig. 15.54). Because the consequences of GVHD are particularly aggressive when there is mismatch of MHC class I or class II antigens, HLA matching between donor and recipient is more critical than in solid organ transplantation. Most transplants are therefore undertaken only when the donor and recipient are HLA-matched siblings or, less frequently, when there is an HLA-matched unrelated donor. Therefore, GVHD mostly occurs in the context of disparities between minor histocompatibility antigens, so immunosuppression must be used in every HSC transplant.
The presence of alloreactive donor T cells can be demonstrated experimentally by the mixed lymphocyte reaction (MLR), in which lymphocytes from a potential donor are mixed with irradiated lymphocytes from the recipient. If the donor lymphocytes contain naive T cells that recognize alloantigens on the recipient lymphocytes, they will proliferate or kill the recipient target cells (Fig. 15.55). However, the limitation of the MLR in the selection of HSC donors is that the test does not accurately quantify alloreactive T cells. A more accurate test is a version of the limiting-dilution assay (see Appendix I, Section A-21), which precisely counts the frequency of alloreactive T cells.
Effector CD4 and CD8 T cells enter host tissues and cause injury T cells circulate in blood to secondary lymphoid tissues. Alloreactive cells interact with dendritic cells and proliferate efferentlymphskinlymphnodebloodvesselAllogeneic hematopoietic cell transplant contains mature and memory T cells