Scientists have investigated the role of regulatory T cells in autoimmune diseases. Regulatory T cells carry the CD4 protein on their surface and they eliminate immune cells that have gone rogue and attack the body's own tissues. But, as Harvey Cantor, an immunologist at the Dana-Farber Cancer Institute, notes, no treatments using regulatory T cells have yet been approved in the treatment of autoimmune diseases. Perhaps another piece of the puzzle involves the newly identified CD8 T cells that target aberrant autoimmune responses.
CD8 T cells are known to kill infected and cancerous cells and had previously been shown in mice to quell autoimmune reactions. This latest research published in Science searched for the effect of their human counterpart on autoimmune and infectious diseases.
Although no human cells have the distinct receptor of these CD8 T cells in mice, some human CD8 T cells do have the KIR protein that is similar. Postdoc Jing Li at Stanford University's School of Medicine investigated whether these KIR CD8 T cells could suppress the immune system.
Researchers in this study found that patients with autoimmune diseases like multiple sclerosis, lupus, and celiac disease had more of these KIR CD8 T cells compared to healthy people. These immune cells also congregated in parts of the body that were targets of the autoimmune process. For example, in patients with celiac disease, more of these cells were found in the small intestine.
Interestingly, the researchers noted, these KIR CD8 T cells were also elevated in people fighting off infections, like COVID-19 and influenza. In the 56 COVID-19 patients examined, those with more severe symptoms had higher levels of KIR-producing cells.
According to immunologist Mark Davis, whose lab at Stanford the research was performed in, these cells may increase in response to a pathogen to kill other T cells that may continue to attack healthy tissues after the pathogen is cleared.
To better understand how these cells work, the investigators examined them in the context of celiac disease. In celiac disease, CD4 T cells promote inflammation when they recognize the gluten protein gliadin. In cell culture studies, Li and his colleagues found that the KIR CD8 T cells killed these CD4 T cells that detected gliadin, seemingly attempting to curb inflammation.
To better understand how protective KIR CD8 T cells are against autoimmunity, the researchers genetically altered mice to have 50% to 75% fewer of these cells. Once exposed to viruses known to trigger autoimmune diseases, these genetically altered mice developed kidney inflammation whereas control mice did not develop any signs of autoimmunity.
Overall, KIR CD8 T cells are said to be rare, making up about 5% of the total pool of CD8 T cells. Their function differs from regulatory T cells in that they kill immune cells that attack healthy tissue whereas regulatory T cells only inhibit these immune cells.