Progress in Liver Transplant Tolerance and Tolerance-Inducing Cellular Therapies

Abstract

Liver transplantation is currently the most effective method for treating end-stage liver disease. However, recipients still need long-term immunosuppressive drug treatment to control allogeneic immune rejection, which may cause various complications and affect the long-term survival of the recipient. Many liver transplant researchers constantly pursue the induction of immune tolerance in liver transplant recipients, immunosuppression withdrawal, and the maintenance of good and stable graft function. Although allogeneic liver transplantation is more tolerated than transplantation of other solid organs, and it shows a certain incidence of spontaneous tolerance, there is still great risk for general recipients. With the gradual progress in our understanding of immune regulatory mechanisms, a variety of immune regulatory cells have been discovered, and good results have been obtained in rodent and non-human primate transplant models. As immune cell therapies can induce long-term stable tolerance, they provide a good prospect for the induction of tolerance in clinical liver transplantation. At present, many transplant centers have carried out tolerance-inducing clinical trials in liver transplant recipients, and some have achieved gratifying results. This article will review the current status of liver transplant tolerance and the research progress of different cellular immunotherapies to induce this tolerance, which can provide more support for future clinical applications.

Regulatory Dendritic Cells, T Cell Tolerance, and Dendritic Cell Therapy for Immunologic Disease

“…While there is a large body of literature from preclinical models that confirms that DCreg can induce antigen-specific T cell tolerance in vivo (50,65,(81)(82)(83), the collective literature addressing the function of human DCreg is less robust. Most studies with human DCreg have been restricted to showing that these DC only poorly activate allogeneic T cell responses in vitro (50).…”

Development of a method for assessing the immunological reactivity of the animal body to prevent the development of pathology in the early stages of postnatal development

“…However, the disadvantage of most methods of assessing the immunological reactivity of the body is their emphasis on the ability to assess the cell-mediated immune response [5][6][7], which in a living organism is especially important for immunodeficiency and immunosuppression [3][4][5][6][7][8]. Immunodeficiency is characterized by a decrease in the ability to elicit an effective immune response.…”

“…Immunodeficiency is characterized by a decrease in the ability to elicit an effective immune response. Such an incomplete immune response or its absence may be a consequence of primary or acquired (secondary) immunodeficiency [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16].…”

“…As for the fetal immune system, it is functionally not yet perfect, areactive and does not enter into an immune conflict with the maternal body. The immune activity of the fetus is formed and develops gradually, depends on the maternal body, [4,7] Guided by these scientific provisions, we assumed that stimulation of immunological reactivity in the mother during pregnancy would influence the formation of the fetal immune system When using the reproductive potential of infected animals during pregnancy, in case of bactero-and/or virusomy, transplacental infection of the fetus occurs with subsequent reproduction of the causative agent in tissues.…”

Detection and Monitoring of Regulatory Immune Cells Following Their Adoptive Transfer in Organ Transplantation

“…The main challenge in clinical testing of regulatory cell therapy, however, is that the in vivo fate and localization of the cell product remains largely unknown which leads to major gaps in understanding of tolerance induction mechanisms and hinders cell therapy protocol design. Non-invasive, accurate, and durable techniques to monitor exogenous cell products after infusion in both pre-clinical and clinical human studies are critical in addressing 1) variability in clinical outcomes, 2) potential cell toxicity and adverse side effects of infusion, 3) anatomic localization and 4) duration and magnitude of desired tolerogenic activity ( 2 ).…”