#MEAction’s Director of Scientific and Medical Outreach, Jaime Seltzer, sat down with Dr. Liisa Selin, MD, PhD, and Dr. Anna Gil, PhD, recipients of an R01 grant to research immune system dysregulation in people with ME/CFS. Selin, a professor of pathology and a person with ME herself, and Gil, a viral immunologist, comprise the two-person Selin lab at the University of Massachusetts T.H. Chan Medical School.
Selin and Gil’s primary area of study involves T cells, white blood cells involved in the immune response to infection. They are particularly concerned with CD4+, CD8+, and CD4+CD8+ (“double positive”) T cells, or cells that express CD4 and/or CD8 markers, which are receptor proteins on the cell’s exterior that affect the cell’s function. CD4+ cells are known as ‘helper cells,’ as they signal CD8+ ‘killer’ cells to destroy a pathogen. Selin and Gil have identified two apparent differences between T cells in healthy controls and those in people with ME/CFS. According to their research, people with ME/CFS have much higher levels of CD4+CD8+ T cells, as well as more exhausted CD8+ T cells.
While Selin and Gil are as yet unsure about the precise functions of CD4+CD8+ cells, they have found that these cells are increased by a factor of 18 in ME/CFS patients as compared to healthy controls. This finding presents a dual opportunity to further understand mechanisms at play in ME/CFS and to study the functions of these double-positive cells more generally, as they are more abundant in people with ME/CFS.
Another area of interest for Selin and Gil is functional immune exhaustion: when immune cells lose some or all of their ability to respond to pathogens, usually in chronic infection but sometimes in cancer. To test the functional exhaustion of CD8+ T cells, Selin and Gil exposed these cells to a specific chemical. Healthy, non-exhausted cells produce certain cytokines in response to this exposure; exhausted cells do not. Selin, working with her own cells, found that only 1-3% of her CD8+ T cells were producing these cytokines. This is in stark contrast to the amount found in healthy controls, which ranges from 50-70%. Selin and Gil hypothesized an antigen (either the pathogen in the original infection or a previously dormant virus) could be at work. It’s also possible that overall metabolic shifts are changing the way these cells function. Selin and Gil applied for an R01 grant from the NIH to research this further and were awarded the grant in 2021.
If Selin and Gil’s findings hold true in larger samples of people with ME/CFS, they would have important implications for treatment. Selin stresses that a multipronged approach to treating ME/CFS is necessary: for example, one must not only consider the original pathogen but long-term changes in metabolism as well. In terms of the infection itself, Selin is looking into Inspiritol which contains naturally-occurring anti-inflammatory compounds, and is intended to relieve oxidative stress, as well as antivirals. However, she emphasizes that various medications may be appropriate for different lingering infections.
Selin and Gil estimate that a paper summarizing their research findings will be published this year.
Recently, the Selin lab helped organize a meeting with Congressmen Jim McGovern (D-MA) and Jamie Raskin (D-MD), as well as researchers and advocates for ME and Long COVID at the U Mass Chan Medical School. Selin spoke about her lab’s research.
ME/CFS research is critically underfunded, and Selin and Gil’s work is no exception. Despite being awarded the R01 grant, they are in need of additional funding to secure adequate resources, incorporate more patient samples, and expand their research in exciting new directions. To support their cutting-edge work, you can donate here.