Suppressor cells will protect against the graft-versus-host reaction
The transplantation of healthy bone marrow stem cells is the only hope for the recovery of many patients with acute myeloid leukemia – a malignant disease in which the production of white blood cells – leukocytes is disrupted (an electron micrograph shows a leukocyte of a patient with acute myeloid leukemia). However, during preliminary radio- or chemotherapy, together with cancer cells, the immune system is completely destroyed, the recovery process of which is so subtle and complex that it can cause not only severe post-transplant reactions, but also the death of the patient.
Mature immune cells of the donor provide protection to the body for several weeks after transplantation. However, at the same time, they can attack the patient's cells that are foreign to them, causing the development of a deadly graft-versus-host reaction (GVHD).
Italian and Israeli scientists have developed a new method to prevent the development of GVHD after bone marrow transplantation, while protecting patients from infections. The method is based on the addition of suppressor T-lymphocytes to the transplant material, which prevent the attack of the donor's killer T-lymphocytes on the recipient's tissues, without violating their ability to fight pathogens. The results of the work were presented by the authors at the 51st Annual Congress of the American Society of Hematology, held on December 5-8 in New Orleans
The problem associated with the "graft versus host" reaction is compounded by the fact that most of the transplants used in the clinic are obtained from donors partially compatible with patients according to the antigen system of the main histocompatibility complex. The selection of a fully compatible donor, with rare exceptions, is an impossible task.
If the donor and recipient are not fully compatible, GVHD can be prevented by introducing large doses of hematopoietic stem cells that turn into mature cells of the immune system already in the recipient's body. This principle was proved in animal experiments by one of the authors of the article, Yair Reisner from the Institute. Weizmann Institute, Rehovot, Israel.
After receiving promising results in working with mice, Reisner, together with researchers from the University of Perugia (Italy), tested the approach on more than 300 patients. The proportion of successful bone marrow transplants of partially compatible donors in the experimental group corresponded to the proportion of successful bone marrow transplants of fully compatible donors found through international registers of potential donors. To reduce the risk of developing GVHD, mature T-lymphocytes were removed from the transplants, which increased the risk of developing dangerous post-transplant infections.
In their latest work, researchers working under the guidance of Massimo Martelli, head of the Department of Hematology and Clinical Immunology at the University of Perugia, injected 28 patients with leukemia with regulatory T-lymphocytes isolated from the donor's blood with the CD4/CD25+ phenotype. Cells of this type reduce the likelihood of an attack by immunocompetent T-lymphocytes on the recipient's tissues and in animal experiments have demonstrated their ability to prevent the development of GVHD. There is also evidence that these cells suppress other immune responses, including autoimmune damage to body tissues, without reducing the ability of immune cells to fight infections.
CD4/CD25+ cells were injected into patients at the end of the course of radio and chemotherapy. After that, they were injected with bone marrow transplants containing both hematopoietic stem cells and mature T-lymphocytes, which are necessary for the body to fight viral and fungal infections before the stem cells form a new functioning immune system.
As a result, GVHD developed only in one of the patients who underwent a full course of therapy. In addition, the researchers state that the recovery of the immune system in patients occurred much faster than after the use of a conventional transplant protocol.
Experts believe that the method proposed by the authors will reduce the post-transplant mortality of patients as a result of severe GVHD or infectious complications.
In addition, most of the potential bone marrow donors, information about which is contained in international registries, are people with white skin color of North European origin. This greatly complicates the search for compatible donors for representatives of other racial and ethnic groups. The new method will expand the possibilities of using partially compatible donors, which can be close relatives of the patient (brothers, sisters, parents). This factor is also important because in acute leukemia, the speed of donor selection is of great importance and often the patient does not have time to search for a donor using international registries.
However, despite all the advantages provided by the new method of transplantation, for its widespread introduction into clinical practice, it is necessary to conduct more extensive and long-term clinical trials.
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of TechnologyReview: Calming Cells Fend Off Immune Attack.
17.12.2009