Very interesting, David. I'm curious how the thymus transplant aspect worked. I can't quite wrap my head around what that would do. Transfer over T cells that are tolerant of the kidney? But wouldn't the host T/B cells recognise the thymus and any derived cells as non-self?
Hey Nathan, thanks for the curiosity and questions! The addition of the thymus transplant is interesting. Admittedly, this part is a bit vague in the NYU interview transcript I used to draft this article.
In a nutshell, the thymus is like a school for our immune system's T cells. By transplanting the pig's thymus, the hypothesis is that it will give the recipient's immune system a crash course on accepting the new pig kidney.
Your concern is correct, i.e., wouldn't our body see this new thymus as an intruder? My understanding is normally yes, but the scientists are relying on the Alpha Gal genetic knockout in the pig to disguise the Thymus, similar to the Kidney. Over time, this "schooling" by the thymus should help the recipient body become more accepting of the pig kidney, reducing the chances of rejection. But here's the catch, the real test will be around the 2-month mark when they'll have a clearer picture of how well the thymus is accepted.
I'll plan to give a follow-up as we get more information!
Thanks David. It's impressive if that works. I found this additional quote just now: '"Dr. Griesemer explained. "So, transplanting the thymus from the pig allows new developing cells in the recipient's body to learn to recognize the pig antigens as their own, and it can potentially lead to a decreased immune response and decreased risk of rejection."'
But this still baffles me. The thymus was embedded within the outer layer of the kidney, apparently. Any T cells undergoing thymic education would do so in the host's own thymus (which, I'm guessing based on the age of the recipient would be largely non-functional anyway), so it's quite impressive if this is implying that any nascent naive T cells can migrate to the transplated thymus for education.
You've really dived deep into this, I appreciate the engagement!
The thymus being embedded within the outer layer of the kidney is interesting. It suggests that the transplanted thymus might be strategically positioned to interact directly with the host's immune cells, particularly those that come into contact with the kidney. You would also imagine the renal system is exposed to a lot of blood (by design). This could potentially enhance the "education" process.
Upon delving deeper into the topic of nascent T cells migrating to the transplanted thymus, I came across some interesting information. While the recipient's own thymus might have diminished functionality, as you've rightly pointed out, the newly transplanted and more active pig thymus could act as a supplementary site for T-cell education. However, one might assume that these lingering nascent T cells would already be mature and potentially reactive. Yet, as highlighted in a review by Sykes (2019), an allogenic transplanted thymus plays a role in eliminating autoreactive T-cells. In such scenarios, these cells aren't retrained but are instead directly removed. This suggests that the transplanted thymus might be facilitating both the maturation and the deletion processes.
Does that help some?
Sykes, M. and Sachs, D.H., 2019. Transplanting organs from pigs to humans. Science immunology, 4(41), p.eaau6298.
Thanks! It looks like the literature has been converging on a few of these strategies for a while, particularly the immune training / selection with allogenic thymus and genetic knockouts (e.g., Alpha Gal). There is a lot to be excited about!
In regards to the 'how and where', this information was not described extensively in the transcript. The how is completely missing, I only manged to find that the thymus was transplanted in the outer layer of the xenogenic kidney.
It seems this positioning is likely strategic / by design to interact directly with the host's immune cells, particularly those that come into contact with the kidney.
I hope I can provide some further clarity here as more information is released.
Very interesting, David. I'm curious how the thymus transplant aspect worked. I can't quite wrap my head around what that would do. Transfer over T cells that are tolerant of the kidney? But wouldn't the host T/B cells recognise the thymus and any derived cells as non-self?
Hey Nathan, thanks for the curiosity and questions! The addition of the thymus transplant is interesting. Admittedly, this part is a bit vague in the NYU interview transcript I used to draft this article.
In a nutshell, the thymus is like a school for our immune system's T cells. By transplanting the pig's thymus, the hypothesis is that it will give the recipient's immune system a crash course on accepting the new pig kidney.
Your concern is correct, i.e., wouldn't our body see this new thymus as an intruder? My understanding is normally yes, but the scientists are relying on the Alpha Gal genetic knockout in the pig to disguise the Thymus, similar to the Kidney. Over time, this "schooling" by the thymus should help the recipient body become more accepting of the pig kidney, reducing the chances of rejection. But here's the catch, the real test will be around the 2-month mark when they'll have a clearer picture of how well the thymus is accepted.
I'll plan to give a follow-up as we get more information!
Thanks David. It's impressive if that works. I found this additional quote just now: '"Dr. Griesemer explained. "So, transplanting the thymus from the pig allows new developing cells in the recipient's body to learn to recognize the pig antigens as their own, and it can potentially lead to a decreased immune response and decreased risk of rejection."'
But this still baffles me. The thymus was embedded within the outer layer of the kidney, apparently. Any T cells undergoing thymic education would do so in the host's own thymus (which, I'm guessing based on the age of the recipient would be largely non-functional anyway), so it's quite impressive if this is implying that any nascent naive T cells can migrate to the transplated thymus for education.
You've really dived deep into this, I appreciate the engagement!
The thymus being embedded within the outer layer of the kidney is interesting. It suggests that the transplanted thymus might be strategically positioned to interact directly with the host's immune cells, particularly those that come into contact with the kidney. You would also imagine the renal system is exposed to a lot of blood (by design). This could potentially enhance the "education" process.
Upon delving deeper into the topic of nascent T cells migrating to the transplanted thymus, I came across some interesting information. While the recipient's own thymus might have diminished functionality, as you've rightly pointed out, the newly transplanted and more active pig thymus could act as a supplementary site for T-cell education. However, one might assume that these lingering nascent T cells would already be mature and potentially reactive. Yet, as highlighted in a review by Sykes (2019), an allogenic transplanted thymus plays a role in eliminating autoreactive T-cells. In such scenarios, these cells aren't retrained but are instead directly removed. This suggests that the transplanted thymus might be facilitating both the maturation and the deletion processes.
Does that help some?
Sykes, M. and Sachs, D.H., 2019. Transplanting organs from pigs to humans. Science immunology, 4(41), p.eaau6298.
That's awesome, good delving and looks like a good review of the topic. I wasn't aware that that could happen with a transplanted thymus. Go science!
Thanks! It looks like the literature has been converging on a few of these strategies for a while, particularly the immune training / selection with allogenic thymus and genetic knockouts (e.g., Alpha Gal). There is a lot to be excited about!
I love this article, I've always wondered how organ transplants worked beyond the human body rejecting them. Always wanted a why. Great Stuff!
David, I'm glad you enjoyed. I plan to keep up with this study so we will likely have an update in the future. There is a lot of interest here!
I’m also curious how and where the thymus was transplanted.
Hi Nastia, great question!
In regards to the 'how and where', this information was not described extensively in the transcript. The how is completely missing, I only manged to find that the thymus was transplanted in the outer layer of the xenogenic kidney.
It seems this positioning is likely strategic / by design to interact directly with the host's immune cells, particularly those that come into contact with the kidney.
I hope I can provide some further clarity here as more information is released.