Preprint Abnormal T-Cell Activation And Cytotoxic T-Cell Frequency Discriminates Symptom Severity In [ME/CFS],2025, Lee, Cliff et al

I wrote earlier that it was a shame that this paper didn't go back and compare to HC and MS in data from the earlier study so we could interpret it better. In the webinar linked above Dr. Cliff also made the same point and said that they hadn't got the full data yet and would likely do that later.
 
I’ve been back over the webinar and parts of the paper and it certainly raises lots of thoughts or half formed questions, particularly in light of the paper Jackie contributed to with @Jonathan Edwards and Jo. That would seem to fit the severe or ‘over sensitive’ ‘over reactive’ immune subtype well. But I also don’t see any clear reason here that it couldn’t fit the mild/moderate too?

Maybe the ‘aging cells’ or ‘viral persistence’ vs ‘heightened activation’ or ‘pro inflammatory’ is only narrative and the differences are subtle and not causative?

Rather than being different mechanisms could there be the same core mechanism but different pathways on this? Or responding to the same thing in slightly differing ways?

It would be interesting to hear more about how these papers and ideas tie together from the authors/experts in this field.
 
wigglethemouse said:
I went back and watched Dr. Cliff's CureME webinar presentation and I realised that there is an awful lot of overlap between mild/moderate and severe ME/CFS despite there being group differences.
Click to expand...
Yes, looking over the paper there seems to be a lot of similarities outside of these very specific differences too.

For instance:

Firstly, we compared the frequencies of T cells (identified as CD3+) and T cell subsets (CD4+ T cells, CD8+ T cells, CD4-CD8- Double Negative (DN) T cells, CD4+CD8+ Double Positive (DP) T cells, CD3+CD56+ NKT-like cells), as well as NK cells (identified as CD3-CD56+) and CD8+CD56+NK cells (“NK8 cells”) in ex vivo PBMCs from people with ME-MM or ME-SA, and found there were no differences between the two clinical groups (Supplemental Figure 2A-2H).
Click to expand...

There was no significant difference in CD4+CD8+MAIT frequency between the two groups.
Click to expand...

There were no significant differences in frequencies of naïve/memory subsets in CD4+ or CD8+ T cells between the ME-MM and ME-SA groups, nor were there any differences in the frequencies of CD57-CD28+, CD57-CD28-, CD57+CD28-or CD57+CD28+ subsets (Supplemental Figure 4).
Click to expand...

I like the questions @wigglethemouse has been been raising.

Hopefully things will make more sense with greater context and information, maybe even after DecodeME, but if not then after other studies of T cell populations. But for now it seems it’s difficult for those of us not deep into immunology, and perhaps also for those who are, to draw too many conclusions, especially on mechanisms or correlation/causation.

It seems like these results are telling us something. But what that something is I’m not sure and it seems quite open to interpretation.
 
hotblack said:
Yes, looking over the paper there seems to be a lot of similarities outside of these very specific differences too.

For instance:
Click to expand...
When I asked Drs Selin/Gil about double positive CD4+CD8+ cells they said that you need to sort the cells first before analysing and that is why the CureME immune paper did not detect differences.

This was the post where I provided more information
 
This was the tweet contents by @Susan K in case you can't access:

Standard flow cytometry doesn't involve cell sorting like the magnet sort FACS. So the latter isolates a much more specific population, & allows sorted cells for further analysis like cytokine secretion Video describing difference, begin at 1 hour, 2 min



The power of the LSHTM study is they had so many samples from criteria-defined #pwme. The downside is they had to use frozen PBMCs, & multiple folks doing sample prep. An intractable problem with the big studies
 
Last edited:
You must log in or register to reply here.
Back
Top Bottom