That would be great if CD8+ TRegs did not have CCR5. The few papers on CD8+ TRegs I've seen indicate they do. As with everything with the body / nature, immunology of T-cell subtypes is very complex, and we have a lot to learn still.

Here are a few articles I've recently skimmed, that may be of interest:

https://www.frontiersin.org/articles/10.3389/...02788/full

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CD8+HLA-DR+ Treg cells which showed great similarities with classical CD4+ cells expressing forkhead box P3 (FOXP3). The shared features included the expression of programmed cell death protein 1 (PD-1), T-cell immunoreceptor with Ig and ITIM domains (TIGIT), C-C chemokine receptor type 4 and 5 (CCR4 and CCR5), low expression of CD127, and a memory and effector-like phenotype

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This population of CD8+ T-Regs does express CCR5. However, they may be exhausted TRegs that don't work very well. In MS and other autoimmune diseases, as you said the TRegs are "lazy" or not working very well anyways. So hopefully it's not that critical to have TRegs home to site of MS lesions, since LL may largely prevent this. Maybe it will be enough to keep the CD4+ T-Cells and macrophages away from the sites of inflammation / lesion in MS.

This paper identifies LAG3+ CD8+ TRegs, doesn't speak about CCR5 on them, but talks about them secreting CCL4 to inhibit immune response, and perhaps allowing persistence of infection in mouse tuberculosis model:

https://www.pnas.org/content/104/19/8029

So, TRegs bad in infection.

Here is another article about CD8+ T-Regs, of the QA-1 variety (3-5% of all CD8 T-cells):

https://www.sciencedirect.com/science/article...7618300312

Unfortunately, they don't talk about CCR5 in that paper.

This review paper talks about CD8+ QA-1 TRegs are very important for self tolerance:

https://www.sciencedirect.com/science/article...2311000509

"Recent advances in analysis of the CD8+ lineage of regulatory T cells (hereafter CD8+ Treg) have underscored the contribution of Qa-1-restricted CD8+ Treg to the maintenance of self-tolerance."

OK, one more for rheumatoid arthritis model: CD8+ TRegs are good for treating this autoimmune disorder:

https://www.jci.org/articles/view/66938

So, we want CD8+ TRegs to control against autoimmune disease. There are several different CD8+ TRegs, and at least some of them have CCR5 on them.


This study talks about in cancer, CCR5 allows TRegs to hone to SCC cancer cells by inhibiting CD8+ cytotoxic T-cells there:

https://mct.aacrjournals.org/content/16/12/2871

So, TRegs bad in cancer.

Again showed here in a cancer oh too near to me, OSCC, where TRegs (of various subtypes, CD4+ FOXP3+, CD8+ FOXP3+, and other) are increased, and keep the body from killing the cancer:

https://pubmed.ncbi.nlm.nih.gov/28833201/

and in infection too, CD8+TRegs are bad, and inhibiting them helps fight off viral infection in mouse models:

https://www.pnas.org/content/110/52/21089


Here again, TRegs bad in pancreatic cancer:

https://www.nature.com/articles/onc2016458

Talks about "~99% of FOXP3+T cells are CD4+Treg cells and <1% are CD8+Treg cells in tumor tissues"

and

Quote:

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CCL5 is involved in the recruitment of Treg cells induced by c-FOXP3. Although CCR5 was also expressed in the effector T cells, its expression level was lower than in Treg cells.36 In combination with the finding that Treg cells exhibited a greater chemotactic response toward CCR5 than the effector T cells,37 it suggested a more important role of the CCL5/CCR5 pathway on Treg cells recruitment than the effector T cells in PDAC.

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Goes back to what Dr. Patterson was saying about receptor density of CCR5.

I still wonder in autoimmunity if LL will be keeping the TRegs away moreso than the CTLs / CD8+ killer T-cells, and how that will work out. We shall see before too long I hope.

Basic take home message for me is that TRegs are bad in infection and cancer, and good in autoimmunity. Hopefully LL will allow them to be distributed appropriately to help in each of these diseases.