Why adult bodies still rely on fetal T cells

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Fetal immune cells are present in adults and have specialized roles during infections, according to new research.

“…we might be able to predict how individuals will respond to infection based on how many fetal cells are present in the adult pool…”

In fact, the first immune cells made in early life are fast-acting first responders to microbes in adulthood. These immune cells—called CD8+ T cells—come in fetal and adult varieties, which originate in separate parts of the body and are hardwired with intrinsically different properties.

The current paradigm is that, around the time of birth, the body switches from making and using fetal T cells to adult T cells to defend itself. Researchers used a unique study design, however, to show that fetal T cells persist into adulthood and have different roles than adult cells in fighting infection.

“This discovery has led to the new idea that we might be able to predict how individuals will respond to infection based on how many fetal cells are present in the adult pool and isolate the fast-acting fetal-derived cells for certain therapeutic interventions, such as infections and cancer immunotherapy,” says Brian Rudd, associate professor of immunology in the College of Veterinary Medicine at Cornell University and the paper’s senior author.

T cells are made in an organ called the thymus, which sits above the heart. In order to make a T cell, the body requires a stem cell, but the origin of these stem cells changes through development. The first stem cells that colonize the fetal thymus come from the fetal liver and give rise to fetal T cells. Around the time of birth, a new wave of stem cells are made in the bone marrow, which then colonize the thymus and give rise to adult T cells.

“What we found is that fetal and adult T cells are intrinsically different,” Rudd says. “The reason for that is they derive from different stem cells, which are genetically distinct.”

In adults, newly formed T cells recognize a signature protein on a pathogen when they first encounter it. That signal then activates the T cells and equips them to fight and proliferate up to 15 times, producing up to 10 million cells in a week. Once they’ve cleared the pathogen, most of those adult T cells die, but a pool of memory cells stores up to 10 percent that survive, allowing for a rapid recall response if that same pathogen were to strike again.

Fetal-derived cells, on the other hand, are generalists and do not form into memory cells. They respond to inflammatory signals and activate faster than adult T cells, allowing them to provide a broad swath of protection against pathogens they don’t specifically recognize, Rudd says.

“It’s the way that the immune system hedges its bet: It has cells that can respond at different rates,” Rudd says.

Previously, scientists had no way of tracking these different types of cells. In the study, the Rudd lab used a special “time-stamp” mouse that allowed them to map the fate of these cells throughout the mouse’s life. A drug (tamoxifen) injected at various stages of life marks the waves of T cells made during different stages of development. The system allowed the researchers to see which cells were present during adulthood.

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“We were able to map cells produced at different stages of life and track their numbers and functions over the life span,” Rudd says. “This led to the discovery that there are developmental layers to an immune response, which has previously gone unnoticed.”

Future work will explore how genetic and environmental factors, such as diet and gut bacteria, may alter the developmental layers in the immune system.

Additional coauthors are from the University of New South Wales in Sydney, Australia.

The National Institutes of Health and the National Health and Medical Research Council in Australia funded the study.

Source: Cornell University