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Developmental biology - Immune Cells

Fetal T cells are first responders to infection in adults

Cornell University research discovers a division of labor among immune cells that fight off invading microorganisms...


The study, published in the journal Cell, finds for the first time that fetal immune cells are present in adults and have specialized roles during infection. In fact, the first immune cells made in early life are fast-acting first responders to microbes in adults.

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, our body switches from making and using fetal T cells into making and using adult T cells to defend itself. But Cornell researchers use a unique study design to show how fetal T cells persist into adulthood but play a different role than adult T cells when fighting infection.

In adults, newly formed T cells can immediately recognize a pathogen protein. They then signal and activate T cells equipping them to proliferate and fight that pathogen up to 15 times, producing up to 10 million T cells in a week. Once the pathogen has been cleared, most adult T cells die. But, up to 10 percent survive to be stored in a pool of memory cells, allowing for a rapid response if the same pathogen strikes again.

"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," explains Brian Rudd PhD, Associate Professor of Immunology at the College of Veterinary Medicine, Cornell University, Ithaca, New York, USA and senior author. Norah Smith, a research associate in Rudd's lab, is the paper's first author.
Fetal-derived cells 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 adds.

Rudd: "It's the way that the immune system hedges its bet. It has cells that can respond at different rates."

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

Highlights
Fate mapping reveals developmental layers in the CD8+ T cell response to infection
The fetal layer of CD8+ T cells exhibits rapid and innate-like functions in adults
The adult layer of CD8+ T cells preferentially gives rise to long-lived memory cells
CD8+ T cells with different developmental origins possess distinct regulomes

Summary
Heterogeneity is a hallmark feature of the adaptive immune system in vertebrates. Following infection, naive T cells differentiate into various subsets of effector and memory T cells, which help to eliminate pathogens and maintain long-term immunity. The current model suggests there is a single lineage of naive T cells that give rise to different populations of effector and memory T cells depending on the type and amounts of stimulation they encounter during infection. Here, we have discovered that multiple sub-populations of cells exist in the naive CD8+ T cell pool that are distinguished by their developmental origin, unique transcriptional profiles, distinct chromatin landscapes, and different kinetics and phenotypes after microbial challenge. These data demonstrate that the naive CD8+ T cell pool is not as homogeneous as previously thought and offers a new framework for explaining the remarkable heterogeneity in the effector and memory T cell subsets that arise after infection.

Authors: Norah L. Smith, Ravi K. Patel, Arnold Reynaldi, Jennifer K. Grenier, Jocelyn Wang, Neva B. Watson, Kito Nzingha, Kristel J. Yee Mon, Seth A. Peng, Andrew Grimson, Miles P. Davenportand Brian D. Rudd.


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

Cornell University has television, ISDN and dedicated Skype/Google+ Hangout studios available for media interviews.


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Jun 21, 2018   Fetal Timeline   Maternal Timeline   News   News Archive




The current immune response model suggests a single type of T cell gives rise to other populations of T cells - depending on type and amount of infectious agents encountered. Now, we find multiple populations of T cells exist, distinguished by developmental origin.
Image credit: Rudd lab, CELL magazine.


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