Immune-suppressing regulatory T cells constantly patrol body

Cambridge scientists have discovered that a type of white blood cell - called a regulatory T cell - constantly moves throughout the body looking for - and suppressing - inflammation and the toxic effects it can have on tissues. The findings - published in the journal Immunity - challenge our understanding of the way that these cells work: previously scientists thought they migrated to an organ and then stayed put. The discovery means we now know how to lay bait to attract them to a site of inflammation - like an asthmatic lung - and then use them to control the condition. Adrian Liston led the team behind the discovery…

Adrian - So we're working on these cells in the immune system that actually shut down the immune system and they shut down inflammation. They start to promote the healing after an infection. We've got some of these cells that are present in our circulation. And then we've also got some of these cells that are present in more or less every organ. So they'll be sitting inside our brain, sitting inside the liver, sitting inside the lung. And what we want to work out is how these cells get there, what they do there, how they're related to each other.

Chris - And I suppose are they all one giant population that just spreads everywhere, like spreading butter across a piece of toast or are they specialised for each of those different domains in the body?

Adrian - Exactly. And for a lot of the immune cells that are present in our body, the ones that are inside organs tend to go into those organs very early in life. They're there before we're born and we'll never get any more of those cells. Now what we found out actually is, for these healing cells, these anti-inflammatory cells that shut down the immune response, these are not specialised per organ. They're not going in during very early developmental life. Instead they're kind of just travelling across our body continuously. They might be going through the blood, they'll pop in, spend a couple of weeks in your brain, they go back into the blood, then they can spend maybe a couple of months in the liver and they're just sort of slowly surveying the whole body, looking for any places where damage could be happening.

Chris - Given that there are millions of these cells and they are tiny, how did you establish that?

Adrian - So one of the things you can do is to take cells from one mouse and we can take the cells that are present in the liver and then we can actually take a gene from jellyfish that makes jellyfish glow green. We can have that present in the cells and then we transfer them into a new mouse. And the interesting thing is that we can then track where those green cells are in the new mouse and we can find that the cells that were in the lung, when you transfer them into a new mouse and you make them green, you can then spot them in the liver or you can spot them in the brain. And this process allows us to track where these cells are over time

Chris - And what's the purpose of that? Why don't they just go somewhere and stay put. There must be a reason why they are on the move like this. And what do you think the implications of this finding are?

Adrian - I think the fact that they move and they travel from organ to organ might be linked to their role as basically the global policemen, they're looking for spots where the immune system is too active, they're looking for spots where there is too much damage and need to shut it down. And that spot changes over time. Sometimes you might have a twisted knee and you've got a really inflamed knee, the muscle is injured and you need to have more cells in there shutting down the inflammation. Another time you've had an infection with a respiratory virus and the immune system has gone in there and done a lot of damage in the process of getting rid of that infection. And afterwards you need to start healing that lung, try to regain that function. So the place where we need these cells is going to be different all the time. And I think having this population that is basically on patrol across the whole body, it allows you to mobilise the forces where you need the most at the point where you need the most. Now from a therapeutic point of view, this is actually great for medicine because now that we know that these cells can move from organ to organ, we've got the potential to directly push them in the place that we want to go to.

Chris - What, you mean like laying bait to pull them in so that you can allure them into an area where you want to drive the inflammation down? Because they'll come in and they'll exert their peacekeeping role.

Adrian - Exactly. Bait's a great way to look at it. Another way you can look at it is giving them the food that they need. So these cells, the anti-inflammatory cells basically constantly need to be fed. They survive on this diet of a protein called interleukin 2. And essentially if you keep on feeding these cells, they thrive and they do their job. But if you starve those cells even for a day or two, then they die off. Now what we can do is if we want to have more of these healing cells in a particular organ, we can simply add a novel drug that we've developed that can produce more of the food for the cells in that particular organ. So we can take a mouse that has got neuroinflammation, they've got inflammatory problems going on in the brain that are really critically damaging their ability to think. And we can give more of this food for the regulatory T cells so that the cells can then expand up in the brain. And if we do that, what we find is that those cells are able to shut down the inflammation and they can also start actively repairing the brain damage. Now ideally we can then move this into the human context because this is what we ultimately want to do. The reason we study disease in mice is so that we can cure disease in humans.

Chris - People often talk about these regulatory T cells in the context of things like asthma as well. So would one possibility with this or one application of this be you inhale some interleukin 2 food for these regulators and pull them into the lungs where they'll damp down that sort of inflammation and they make people's asthma better.

Adrian - I think that's a strong possibility. The food that we're giving them can be applied in an aerosol. We can give it into their lungs. And if we do that, we see more of these cells build up in the lung. Now the regulatory T cells that we're dealing with, they are really quite potent. They are able to express a whole bunch of different medicines essentially, and they can tackle different inflammation and what they sense is the type of inflammation that's going on. And so they might see a situation where the lungs are damaged by an infection and they can heal that way. But also if they see the damage that's going on in asthma or chronic lung disease, they'll turn on different medicines and start the healing process there.