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ME/CFS and related chronic complex diseases

OMF-funded research: T cells and molecular immunology

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It’s #OMFScienceWednesday! For the next few weeks, we will be describing the research projects that OMF is funding all over the world. The first project is about T cells and molecular immunology of ME/CFS, at the ME/CFS Collaborative Research Center at Stanford under the direction of Dr. Ron Davis. This project is a collaboration with Stanford professors Dr. Mark Davis, an expert in immunology, and Dr. Lars Steinmetz, an expert in genetics and gene expression. We are hopeful that it will provide a new level of understanding into the immunological basis of ME/CFS.

Many studies have highlighted issues with the immune system in ME/CFS, ranging from altered cytokines to impaired NK cell function. Recently, Dr. Mark Davis’ team discovered evidence of clonal T cell expansion in ME/CFS patients – meaning that the killer T cells responsible for eliminating infected cells are making copies of themselves. Expansion happens when there is an active infection that the immune system is fighting, but it can also happen in autoimmunity, when the immune system mistakenly attacks the body’s own cells. Dr. Steinmetz’s team has developed new technologies to sequence single T cells and measure their gene expression. Understanding the behavior of these expanded T cells and what they are targeting will help us to better understand – and hopefully treat – ME/CFS. For example, it’s possible that some patients’ T cells are reacting to a microbial infection, and that some may have a truly autoimmune disease – which could in turn point to treatment via antimicrobials or immunomodulation.

To explore these possibilities, this project includes the following objectives, in a group of 25 ME/CFS patients this year:

  1. Capturing and sequencing single T cells using these new technologies for identifying clonally expanded T cells and measuring their expression of thousands of genes, to understand their function in ME/CFS. The technologies were pioneered in tuberculosis patients, and the team is now hard at work optimizing them for ME/CFS patient samples.
  2. Sequencing key immune-related genes: HLA and KIR. These genes – whose variants are associated with risk for infectious and autoimmune disease – are very difficult to sequence using traditional methods, so Dr. Ron Davis and his collaborators have developed better methods! Applying them here may help to interpret the other immunological data from this project.
  3. Identifying the targets of expanded T cells. These may be infectious or autoimmune targets, and as described above, identifying them will reveal important insights into ME/CFS and its effects on the immune system of these patients.

Read last week’s post for more on what T cells do in the immune system.

Check out this video of how T cells patrol the body for threats including cancer cells and infected cells: