Selin Lab

Thank you for sharing this. I read the Health Rising lay summary.

I wonder how the remarkably clean perferin result and T cell exhaustion hypothesis relates to the new Zhang paper that comes at it from the genetics start point. Do the two converge at all?
 
From Facebook


ICYMI: Read the Summary of Our Webinar On Immune Dysfunction & T Cell Exhaustion

Last month we hosted the webinar “Immune Dysfunction & T-Cell Exhaustion via Single Cell Immune Profiling in ME/CFS & Long COVID,” with Solve Ramsay Research Grant Winners Dr. Liisa Selin and Dr. Anna Gil (Selin Lab), Roshan Kumar, PhD (HiFiBiO Therapeutics), and patient advocates Rivka Solomon, MS, and Megan L. Fitzgerald, PhD.

It’s one of our most viewed webinars on YouTube, and it caught the attention of health journalist Cort Johnson. He wrote about it at length in his Health Rising blog here:
https://ow.ly/1pY750VWGqC

The webinar covered complex scientific information and our panelists kindly provided a layperson-friendly summary describing the defects these investigators have found in cells of the immune system from people with ME/CFS and Long COVID -- which they believe are at the core of these conditions.

You can read their summary here:
https://ow.ly/Vchi50VWGqF

and watch the webinar again here:
https://ow.ly/sr7x50VWGqE
 
Dolphin said:
The webinar covered complex scientific information and our panelists kindly provided a layperson-friendly summary describing the defects these investigators have found in cells of the immune system from people with ME/CFS and Long COVID -- which they believe are at the core of these conditions.

You can read their summary here:
https://ow.ly/Vchi50VWGqF
Click to expand...

The written summary is good and actually adds some new information. Here they define T cell exhaustion (@Jonathan Edwards), not necessarily by markers but by function. And they identified increased activation markers in patient CD8+ T cells.
Compared to healthy controls, exhausted CD8+ T cells in patients have decreased production of IFNɣ, TNFɑ, and perforin/granzyme, which are all molecules important in controlling any new or persistent infections present such as EBV or CMV. And, we show increased activation markers in patient CD8+ T cells.
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EDIT: Would decreased production of IFNɣ in lab tests indicate that the T cells have been releasing too much IFNɣ in vivo, perhaps supporting the JE hypothesis?

In the webinar I don't think they mentioned the collaboration with Dr. Dario Ghersi at the University of Nebraska at Omaha, who is an expert in TcR repertoire analysis and target antigen prediction.
By examining the TcR sequences of patients, we can identify groups of T cells that have expanded in response to antigen stimulation. Both the dysfunctional CD4+CD8+ and CD8+ T cell subsets in patients show evidence of clonal expansions to an unknown antigen, which may be a viral or autoantigen. This work is being done in collaboration with Dr. Dario Ghersi at the University of Nebraska at Omaha, who is an expert in TcR repertoire analysis and target antigen prediction. With the combination of single-cell RNA and TcR sequencing data from dysfunctional T cell subsets in patients, we are uniquely positioned to identify the target antigens driving this response which will shed light on underlying disease mechanisms. Altogether, these results suggest that ME/CFS and LC patients have an ongoing, over-activation of CD8+ T cells by some persistent antigen, leading to T cell exhaustion. This is similar to what is observed in a person with chronic viral infections or in tumor environments.
Click to expand...
 
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wigglethemouse said:
In the webinar I don't think they mentioned the collaboration with Dr. Dario Ghersi at the University of Nebraska at Omaha, who is an expert in TcR repertoire analysis and target antigen prediction.
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Does anyone know if Chris Ponting's @Chris Ponting colleagues published their findings anywhere on T cell receptor sequencing in ME/CFS - I seem to remember it was a null result. Perhaps access to the data or a chat with the researcher that did the work could help Dr. Dario Ghersi's work. Or maybe there was never such a project and it was B cell only.

@Simon M Perhaps you can remember?
 
wigglethemouse said:
The written summary is good and actually adds some new information. Here they define T cell exhaustion (@Jonathan Edwards), not necessarily by markers but by function. And they identified increased activation markers in patient CD8+ T cells.
Click to expand...

I have discussed the exhausted T cell idea with Jo Cambridge at length. She agrees that it may well be a red herring. The idea defining 'exhaustion' is that cells fail to respond to standard stimuli because they have some past history of being activated. The markers are supposed to point to this. But this begs a hundred and one questions about how you know that these cells have this past history and whether the 'standard stimuli' are relevant for these particular cells. Maybe the cells that usually respond to 'standard' stimuli are off busy somewhere else and the blood is full of other cells that have other jobs to do. T cells divide into a bewildering array of overlapping, stratified functional subsets which we still do not fully understand.

It is interesting if a group has found some functional differences in a blood population of CD8 cells but worth remembering that there have been at least a score of papers in the past looking at lymphocyte populations in blood in ME/CFS and pretty much every study finds something different which may just be a chance finding.

I would hope that there are some differences to find, using techniques like short term co-culture perhaps, but I am a bit sceptical that this lab suddenly joining the party is going to strike gold with a few preliminary experiments.
 
wigglethemouse said:
Does anyone know if Chris Ponting's @Chris Ponting colleagues published their findings anywhere on T cell receptor sequencing in ME/CFS - I seem to remember it was a null result. Perhaps access to the data or a chat with the researcher that did the work could help Dr. Dario Ghersi's work. Or maybe there was never such a project and it was B cell only.
Click to expand...

There was certainly a null result from Chris's group on T cell clonal expansion. I would be very sceptical that anyone will find antigen specific clones here. This is a very standard tunnel vision T cell immunology approach that by and large never pans out to anything. About the only disease where I think it might work is tuberculosis, and for good reason.
 
wigglethemouse said:
Does anyone know if Chris Ponting's @Chris Ponting colleagues published their findings anywhere on T cell receptor sequencing in ME/CFS - I seem to remember it was a null result. Perhaps access to the data or a chat with the researcher that did the work could help Dr. Dario Ghersi's work. Or maybe there was never such a project and it was B cell only.

@Simon M Perhaps you can remember?
Click to expand...

Comparison of T-cell Receptor Diversity of people with Myalgic Encephalomyelitis versus controls, 2023, Dibble, Ponting et al
 
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