Working together to unleash killer T cells

A research team led by the Walter and Eliza Hall Institute has discovered how two pathways cooperate to unleash the immune system’s assassins, called cytotoxic or ‘killer’ T cells. Their findings, published in the journal Nature Immunology, could be harnessed in the future to improve the treatment of chronic infections or cancer.

Killer T cells detect, attack and kill abnormal cells in our body, such as those that are infected with viruses or have undergone cancerous changes. The formation of killer T cells during immune responses is guided by signals, called cytokines, released by other immune cells.

“These signals are transmitted to two separate regulator proteins within the T cell, called Blimp-1 and T-bet,” said Dr Axel Kallies, the corresponding author on the study. “For several years it has been known that these molecules both contribute to the formation of killer T cells, but we haven’t understood how they work together.”

Using genetic approaches and transcriptional profiling of antigen-specific CD8 killer T cells, the researchers showed that the combination of both cytokine signals triggers the formation of the killer cells that can fight a viral infection. If one of these signals is lost, the immune response is dampened but still functional.

“This creates a buffered system that helps the organism to fight different types of infections or cancerous cells,” said Dr Kallies. “It’s a great example of how our body has checks and balances in place to ensure the immune system is switched on at the right time — such as during an infection — but can be toned down at other times to avoid a damaging attack on healthy cells.”

With CD8 T cells having been central to recent breakthroughs in cancer immunotherapy, Dr Kallies hopes his research into killer T cell formation will lay the groundwork for future advances. “Our team is now looking at how we can apply our discoveries to approaches aimed at improving cancer therapies,” he said.