A trick against rejection
Organ transplantation is improved by malignant trickery
Kirill Stasevich, Science and Life (nkj.ru )
One of the biggest problems in transplantology is the rejection of transplanted tissues. Since the same proteins are synthesized in different ways in different people, the immune system after transplantation sees that something has appeared in the body that does not look like ordinary body cells. As a result, the immune system perceives new tissues as potentially dangerous aliens and begins to fight them.
They try to overcome rejection with the help of immunosuppressive agents, but if we suppress the activity of the immune system, dangerous side effects occur: after all, the immune system protects us from infections and from malignant cells. So here we have to look for some other ways. For example, we once described a rather ingenious method when an organ for transplantation is grown in interspecific chimeras: stem cells of another species are transplanted into the body of one species during embryonic development - such a trick helps the immune system get used to someone else's organ. Another option is to use transplants with chitosan, which calms the immune response.
But perhaps the most unusual method of all that research groups around the world are developing is what the University of Pittsburgh staff is offering: they managed to prevent rejection with the help of a trick used by cancer cells.
As you know, the immune system must destroy malignant tumors, but unfortunately, tumors have different ways to help escape from an immune attack: cancer cells become invisible to immune cells and use molecular signals that suppress immune activity. In the immune system itself there are fuses that control its activity, and among these fuses regulatory T-lymphocytes play an important role. Cancer cells are able to call regulatory T-lymphocytes to help with the help of the CCL22 protein – "fuse" cells come to the tumor and make other immune cells passive, not responding to cancer.
As you know, the immune system must destroy malignant tumors, but tumors, unfortunately, have different ways to help escape from an immune attack: cancer cells become invisible to immune cells and use molecular signals that suppress immune activity. In the immune system itself, there are fuses that control its activity, and among these fuses, regulatory T-lymphocytes play an important role. Cancer cells are able to call regulatory T-lymphocytes to help with the help of the CCL22 protein – "fuse" cells come to the tumor and make other immune cells passive, not responding to cancer.
And so it was decided to use the CCL22 protein in experiments with leg transplantation: the hind leg from a gray rat was transplanted to a white rat.
All the rats tested were given immunosuppressive drugs for several weeks; but some, in addition, were injected under the skin of the transplanted leg with different doses of nanoparticles with CCL22 or just CCL22 (or, as a control, nanoparticles without CCL22). In the first 50 days after transplantation, all rats that did not receive nanoparticles with the CCL22 protein had new legs rejected. CCL22 in nanoparticles came out of them gradually and acted longer. An article in Science Advances (Fisher et al., In situ recruitment of regulatory T cells promotes donor-specific tolerance in vascularized composite allotransplantation) states that two injections of nanoparticles with CCL22 preserved transplanted legs for more than 200 days (while moderate doses of nanoparticles were more effective than high ones).
As expected, there were more regulatory T lymphocytes in the transplanted paws, and inflammatory genes were less active in the leg tissues than in rats that did not receive nanoparticles with CCL22. In addition, the CCL22 protein helped skin fragments to take root, which were transplanted from the same rats as the paws, and the skin took root even without the help of immunosuppressors. If the skin was transplanted from some other rats - not from those from whom the legs were taken – then the skin was rejected.
That is, immunity with the help of the CCL22 protein did not fall asleep at all, namely, it got used to specific foreign tissues, learned to recognize them as its own. It is possible that such a trick, borrowed from cancerous tumors, will really help solve the problems associated with organ rejection – if, of course, this method will prove itself well in further experiments.
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