The trend for transplant medicine development: induction of immune tolerance or regulation of immune response?

• Published in: Transplantologii͡a Vol. 14; no. 2; pp. 195 - 209
• Main Authors: Kildyushevsky, A. V., Moysyuk, Ya. G., Mitina, T. A., Kofiadi, I. A., Chuksina, Yu. Yu
• Format: Journal Article
• Language: English
• Published: N.V. Sklifosovsky Research Institute for Emergency Medicine of Moscow Healthcare Department 14.06.2022
• Subjects: cell chimerism; graft rejection; graft versus host disease; immune tolerance; immunosuppression; regulatory cells; solid organ transplantation
• ISSN: 2074-0506; 2542-0909
• DOI: 10.23873/2074-0506-2022-14-2-195-209

One of the greatest medical advances of the last century has been the introduction of organ transplantation. However, despite the considerable potential of transplantation as often the only therapy for severe diseases, the toxicity of immunosuppressive drugs supporting the transplant remains a serious problem for its further development. Modification of immune response in order to form tolerance to the transplanted organ can play an important role on the way to minimize immunosuppression. Successful cases of withdrawal of immunosuppressive drugs for medical reasons in kidney and liver transplantation recorded in the literature, as well as the results obtained in the process of modeling such a situation in the experiment, prove that achieving tolerance in organ transplantation is fundamentally possible. The aim of this review is to investigate the ways of immunologic suppression and fundamental mechanisms of immunologic tolerance in the field of transplantation and to review the latest clinical achievements in this respect. The review describes various approaches to the induction of central tolerance in solid organ transplantation implemented in the framework of the original clinical protocols. Special attention is given to a new direction in transplantation medicine – cell technologies providing tolerogenic effect by means of peripheral mechanisms activation, in particular due to activation of suppressor function of regulatory T cells. We draw the attention to the advantages and disadvantages of these two trends. Which of them is preferable? In which direction will scientific thought be developed for realization of the long-term goal of transplantologists: to avoid allograft rejection without affecting the physiological homeostasis of the body? Possible answers to these questions are discussed in this review.