In 1992, researchers discovered a type of T cell in mice that targets and destroys rogue T cells involved in autoimmune reactions (1). The discovery sparked hope for a new cell therapy to treat autoimmune disease; but if there was a human cell equivalent, it did not have the same characteristic receptors, so it remained undetected. Now, thirty years later, researchers have finally found these cells in humans, bringing this specialized T cell therapy one step closer to reality (2).
The newly discovered human T cells, KIR+ T cells, carry the killer cell immunoglobulin-like receptor (KIR+), which helps them identify pathogens. But on KIR+ T cells, the receptor adopts a new function.
“[The discovery] could have a great impact on these autoimmune diseases,” said Kerry Campbell, an immunologist at the Fox Chase Cancer Center who was not involved in the study.
Autoimmunity is caused by T cell malfunction. In celiac disease, rogue T cells ignite an intense inflammatory response against gluten proteins. Jing Li and Maxim Zaslavsky at Stanford University wondered if KIR+ T cells respond to this autoimmune reaction. To test this, they checked if KIR+ T cells were more abundant in the guts of patients with celiac disease when they ate gluten or ate gluten free diets. The scientists found more KIR+ T cells in the patients who ate gluten. Those cells directly killed rogue celiac disease-causing T cells in an attempt to regulate the autoimmune response.
Zaslavsky used RNA sequencing to analyze patient blood samples and uncover the diversity of roles that KIR+ T cells may play in disease. These experiments demonstrated that KIR+ T cells respond broadly to a wide range of autoimmune conditions including celiac disease, multiple sclerosis, and systemic lupus erythematosus. Zaslavsky hypothesized that rather than being a flag for a specific disease, KIR+ T cells likely play a role in the immunological tolerance that stops self-reactive T cells from causing harm.
“We can investigate whether [KIR+ T cells] also target other kinds of pathogenic cells,” said Li. “The final aim is [to find out] whether we can target these cells to treat autoimmune disease or other kinds of diseases that these cells play a role in.
Zaslavsky and Li also found these KIR+ T cells in certain patients with infectious diseases including COVID-19. Patients with more severe disease mounted a stronger KIR+ T cell response than patients with mild disease, possibly to tackle the larger population of rogue T cells in these patients.
“Holding back the immune system is an important thing,” said Campbell. “There's just a lot more that has to be worked out here as far as what's really there, what these T cells are really doing. I think they've defined one little aspect here.”
The authors of the study acknowledged that there is still more to learn about this new class of T cells, but said that this study is an important step forward in the path to understanding autoimmune reactions and how to treat them.
“We've characterized the mechanisms for this new autoimmune regulatory system. And hopefully, it will open up the path to treatments and to therapy for autoimmune conditions,” Zaslavsky said.
References
- Chari, S. Explained: How do autoimmune disorders arise? Drug Discovery News (2022). Available at: https://www.drugdiscoverynews.com/explained-how-do-autoimmune-disorders-arise-15405. (Accessed: 21st October 2022)
- Li, J, and Zaslavsky, M, et al. KIR+CD8+ T cells suppress pathogenic T cells and are active in autoimmune diseases and COVID-19. Science 376, eabi9591 (2022).
