A new type of killer T-cell can stop attacks on healthy tissue

It could prevent autoimmune diseases.
Derya Ozdemir
A newly identified class of T cells. David Scharf/Science

A team of scientists has discovered a brand new form of human T cell that suppresses attacks on healthy tissues, which could lead to treatments for illnesses ranging from lupus to cancer.

In case you forgot, T cells are one of the most significant white blood cells in the immune system, playing a crucial role in adaptive immune response. They can kill diseased or malignant cells; however, studies in mice have shown that some of these cells may also kill T cells responsible for orchestrating autoimmune responses.

For years, scientists have believed that humans share the same cells, but until now, no one had been able to verify their existence.

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The newly discovered class of T cells in the human immune system may be capable of killing other T cells, which would aid in the healing of infections and reducing autoimmune disorders.

"It’s a major step forward in understanding how the immune response and autoimmunity are regulated," immunologist Harvey Cantor of the Dana-Farber Cancer Institute, who wasn’t involved in the work, told Science.

A new class of killer T cells

Mice and people use one type of regulatory T cell called Tregs, which carry the CD4 and prevent autoimmune attacks. The newer enforcers belong to a subset of T cells known as CD8 T cells, which have a different surface protein and are most known for their ability to eliminate contaminated or malignant cells.

One stumbling block was that humans lack the unique receptors that distinguish the CD8 cells in mice. Human CD8 T cells, on the other hand, have KIR proteins, which are similar receptors. 

Jing Li, a postdoc in immunologist Mark Davis's lab at Stanford University's School of Medicine, and colleagues evaluated the number of these human cells in patients with autoimmune illnesses like multiple sclerosis, lupus, and celiac disease to see if they are immunological inhibitors, and saw that the cells were more abundant in patients' blood than in healthy people's blood.

The cells seemed to gather in regions of the body that had been injured by the autoimmune response like the joints in people with rheumatoid arthritis and the small intestine in people with celiac disease, according to the study published in Science. Similar surges of the KIR-producing T cells in people fighting infections were also detected in 56 COVID-19 patients: the sicker the patients were, the more of the cells they harbored.

  

The human counterparts to the rodent immune regulators? 

To get the study a step further and learn more about the cells' function in autoimmune, the scientists focused on celiac disease and saw that helper T cells identified the gluten proteins and released chemicals that cause inflammation, while CD8 T cells containing KIR proteins destroyed those helper T cells in cell culture tests.

The researchers also looked at genetically altered mice that had 50 percent to 75 percent fewer suppressive CD8 cells than normal mice to see how much protection the cells provide against autoimmunity. The rodents experienced kidney inflammation after being exposed to viruses that can cause autoimmune illness. Control mice, on the other hand, showed no signs of autoimmune illness after infection.

Based on these experiments, the paper provides solid data that these cells exist in humans, and this could indicate that techniques that enhance the number of cells in the body may aid in the treatment of autoimmune diseases, according to immunologist Stephen Jameson of the University of Minnesota Medical School.

Study Abstract:
Here we find that CD8+ T cells expressing inhibitory killer cell immunoglobulin-like receptors (KIRs) are the human equivalent of Ly49+CD8+ regulatory T cells in mice and are increased in the blood and inflamed tissues of patients with a variety of autoimmune diseases. Moreover, these CD8+ T cells efficiently eliminated pathogenic gliadin-specific CD4+ T cells from celiac disease patients’ leukocytes in vitro. We also find elevated levels of KIR+CD8+ T cells, but not CD4+ regulatory T cells, in COVID-19 patients, which correlated with disease severity and vasculitis. Selective ablation of Ly49+CD8+ T cells in virus-infected mice led to autoimmunity post-infection. Our results indicate that in both species, these regulatory CD8+ T cells act uniquely to suppress pathogenic T cells in autoimmune and infectious diseases.

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