Tissue-trained T cells account for swift and tailored immune responses

Sanquin researchers demonstrated that during a second infection with a pathogen, the immune response initiates within the tissue and then extends throughout the body. This process shapes the immune repertoire, and may adapt our immune system to more efficiently respond to invading pathogens. These findings may have important implications for cancer treatment, in particular adoptive cell therapy. The results are published in Nature immunology.

Our body is frequently exposed to pathogens, including viruses and bacteria. They enter the body through barrier tissues, such as the skin, lungs, and intestine. In response to these infections, specialized immune cells are formed in the barrier tissues, so called tissue-resident memory T cells. These immune cells take up permanent residence in the tissues and act as local guardians against subsequent infections with the same pathogens.

From tissue to bloodstream

Immune responses against a secondary encounter with a pathogen are faster than the initial response, but the reasons for this have long been incompletely understood. Researcher Felix Behr: “We have found that the T cells in the tissue quickly react to reinfection and expand locally. This enables an accelerated immune response that directly starts in the infected tissue instead of in the distant lymph nodes. To our surprise we saw that some of the local T cells also left the tissue and moved into the bloodstream in response to the reinfection. So these former tissue-resident T cells contributed to immune responses throughout the body”.

Cancer treatment

Importantly, these tissue-experienced T cells persisted in the blood long after the pathogen was cleared. As these T cells were trained in the tissues, they may provide enhanced protection by mounting tissue-tailored immune responses. “Indeed, we found that T cells in the blood with a history of tissue residence provide improved protection against a subsequent infection”, Behr concludes.

Given that novel cancer therapy approaches rely on the responses of T cells from (tumor) tissues, our findings may also have important implications in the context of cancer treatment, in particular adoptive cell therapy.