Kidney T cells subdue organ transplant rejection
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Since the first organ transplants were carried out over half a century ago, these surgeries have gone on to save thousands of lives. But with a few rare exceptions most transplants are still dogged by the fact that we’re introducing foreign tissue into the body, which usually provokes an immune response necessitating management with immune-suppressing drugs; which have side effects of course. But there is a way to transplant organs without needing to resort to immunosuppression. It was discovered over a decade ago that giving people a bone marrow transplant alongside a kidney from the same donor seemed to be able to reprogramme the immune system to accept the new tissue without rejecting it. But it didn’t work for other organs. Now a team in the US have made an extraordinary discovery: if you do a bone marrow transplant, and move in another organ, like a heart, but you also throw in a kidney for good measure, then it works. So there’s something special about the ability of the kidney to control immunity, and the team behind the work suspect it’s down to a family of immune regulating T cells that are common in the kidney. The findings have just been published in Science Translational Medicine, and we asked John Trowsdale, an immunologist at the University of Cambridge, to take a look at the paper for us…
John - Some people lose organs for various reasons and they need a donor organ. Now the problem though, it's not just a surgery, which is incredible. The immune system rejects any organ from another person that is genetically different to you. And so what clinicians try to do is to try to match, as far as they can, the tissue from the donor organ with the recipient. Even if you do match, quite often you've got to use certain drugs to suppress the immune system so it doesn't destroy the organ.
Chris - And there presumably are side effects of doing that because the immune system's there for a reason. So if we dial it down with these drugs, you're going to have potentially some comeback.
John - Absolutely. You can get more cancer with some of these drugs. And of course, because you're dampening down the immune system, you're more prone to infections.
Chris - So the ideal outcome would be if we could do these sorts of transplants but not need to do that to the immune system.
John - Absolutely. The alternative then is to perform a bone marrow transplant. In other words, you actually take the immune system from the donor at the same time that you take the organ. You effectively replace the bulk of the immune system with that of the donor. So in principle, it shouldn't recognise the organ when that's transplanted. What the recipient ends up with is a kind of chimera, if you like. That individual has the immune system of somebody else circulating in their blood.
Chris - And will this work for any organ?
John - Well, this is the key to this paper because they tried with the heart and they said, 'hold on a minute, we can do it for the kidney, but the heart gets rejected. Now why is that? I know, let's put in the kidney together with the heart and see what happens.' They did that double transplant. So they put the kidney and the heart in from the same donor at the same time and then, lo and behold, they found that the heart was not rejected.
Chris - So there's something special about a kidney being there that then makes it work for other organs?
John - There is, but there's one key issue I should mention. If you put in the kidney from one individual and a heart from a different individual, that heart is rejected. This is specific to the immune system from that one individual that's been donated.
Chris - There must be something about the kidney that it has the ability to reprogram the immune system or there's some other kind of cells in there which are doing something special in the kidney and they can come out and do the same job in the heart.
John - That's what the authors of this paper speculate. They suggest that there are some special cells in the kidney. They're called regulatory T cells and their role is to suppress the immune system. So the immune system is in a fine balance. There are the cells that attack organs or tumours and there are cells that actually suppress that. And they're in a fine balance and it appears that the, the kidney contains some cells that are these regulatory T cells and those regulatory T cells go through the body, through the blood and actually manage to condition the heart if you like, so that it actually is not rejected if you put the kidney in at the same time. But as I say, there's specificity here because if you put in a foreign heart, it gets rejected.
Chris - What is special about the kidney though? Because if they're just cells and they can go anywhere in the body, why do they have to be in a kidney to make them then come out and tell the body what to do with the heart?
John - Well, that's for the future and I think that this is obviously where this paper is heading. We want to know what the magic ingredient is so we can actually do this without undergoing all this surgery. With a kidney under heart. It's difficult enough to undergo heart surgery without having a kidney transplant as well. In fact, if you could get the cells from blood, as you say if they're everywhere, you might be able to Identify these cells from blood and put them IN at the same time. It'd be much more convenient.
Chris - Do you think there's something special about the kidney, that it's got some special structure in there we haven't discovered yet, or some other kind of cell that attracts, like a magnet, these special regulatory T cells and that's why the kidney's a particular focus? Or do you think there's something else going on that it is in some way controlling the immune system involving these cells, but there's something else special about the kidney? We haven't yet discovered what that is.
John - The short answer is I don't really know, I'm afraid. I think all those ideas that you propose are feasible. This study takes an awful long time. They waited five years to make sure those hearts were not rejected. What's also fascinating, I might add, is that they also found that you could graft skin from the donor to the recipient and it was not, in most cases, rejected. That's the holy grail of transplantation if you like. If you can take skin from one individual and transplant it to another and it's accepted, then that is quite remarkable. And so the tolerance they obtained in these experiments was profound. And if you can actually identify the cells responsible for that and manipulate those in future, I think that will save an awful lot of heartache for a number of people.
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