Guys Let's Focus on the latest science here

[ljimbo423]

have never come across a "Th1 exhaustion" hypothesis. Did you read about this somewhere?

I read about immune exhaustion in cfs here-

The researchers reported that patients were flush with cytokines and chemokines until around the three-year mark -- suggesting an over-activated immune response in that phase of the illness; thereafter the immune system showed evidence of "exhaustion," and levels of immune molecules dropped

Although they don't say th1 immune exhaustion, I made some connections myself that made sense, at least to me. Because high levels of viruses or titers are found in many with cfs and so many, but not all, catch more than the average amounts of colds and flu's, etc. I am assuming it is the th1 arm that becomes exhausted, at least in some.

 

[ljimbo423]

Is this what you were thinking about @ljimbo423 when you mentioned "Th1 exhaustion"?

That seems to be the same basic principle, although I am thinking it applies to more than just the T cells, like the NK cells also, maybe more. I'm not that familiar with the immune system but so many with cfs have low NK cell cytotoxicity too. I think that's also from exhaustion.

 

[kangaSue]

I don't remember coming across the concept of "T-cell exhaustion" before

Some Australian research in a small IBS study recently reported finding that all the patients with diarrhoea-predominant irritable bowel syndrome (IBS-D) were found to have the same kind of exhaustion in their T-cells that they expect to see in chronic infections.
https://www.adelaide.edu.au/news/news92984.html

 

[nandixon]

Full text for the IBS study is here (PDF download).

 

[kangaSue]

Low dose interleukin-2, IL-2 (aldesleukin) crops up in looking for a therapy to treat T-cell exhaustion. Proof-of-concept clinical trials have shown that low-dose IL-2 can control autoimmune diseases and inflammation.
http://www.nature.com/nri/journal/v15/n5/abs/nri3823.html
http://diabetes.diabetesjournals.org/content/64/6/1912
https://www.ncbi.nlm.nih.gov/pubmed/27734211

 

[kangaSue]

http://www.jci.org/articles/view/67008
[The inhibitory receptor programmed cell death 1 (PD-1) plays a major role in functional exhaustion of T cells during chronic infections and cancer, and recent clinical data suggest that blockade of the PD-1 pathway is an effective immunotherapy in treating certain cancers. Thus, it is important to define combinatorial approaches that increase the efficacy of PD-1 blockade. To address this issue, we examined the effect of IL-2 and PD-1 ligand 1 (PD-L1) blockade in the mouse model of chronic lymphocytic choriomeningitis virus (LCMV) infection. We found that low-dose IL-2 administration alone enhanced CD8+ T cell responses in chronically infected mice. IL-2 treatment also decreased inhibitory receptor levels on virus-specific CD8+ T cells and increased expression of CD127 and CD44, resulting in a phenotype resembling that of memory T cells. Surprisingly, IL-2 therapy had only a minimal effect on reducing viral load. However, combining IL-2 treatment with blockade of the PD-1 inhibitory pathway had striking synergistic effects in enhancing virus-specific CD8+ T cell responses and decreasing viral load. Interestingly, this reduction in viral load occurred despite increased numbers of Tregs. These results suggest that combined IL-2 therapy and PD-L1 blockade merits consideration as a regimen for treating human chronic infections and cancer.]

 

[wastwater]

Is TH17 important then