Amazing stuff! How the immune system in mammals after birth develops is one of those marvels of life.
"... In a new study, ... researchers found that one type of immune cell in newborns — a white blood cell known as a CD8+ T cell (or a cytotoxic T cell) — is “primed and ready” to fight. Within hours of sensing a threat, researchers say, these cells activate and mount a strong, albeit short-lived, defense. ...
CD8+ T cells are critical for fighting viruses and cancer. But there’s a lot known about how they work in adults, the role they play in newborns and infants has been less clear.
For newborns, the moment of birth marks a dramatic shift, as they move from a sterile womb to an environment full of microbes. Their immune systems must quickly learn to fight infections while avoiding excessive inflammation that could damage their developing organs. But how that balance is achieved — and why it sometimes fails — remains poorly understood. ...
Through these tests, the researchers discovered that CD8+ T cells, even at this early stage, are poised to fight infections in newborns. Within hours of sensing a threat, these cells switch on and use extra glycolytic energy and release powerful defenders like TNFα, a chemical messenger that induces inflammation. They also found that many of the CD8+ T cells die off after their initial burst, likely to prevent ongoing inflammation that could damage a newborn’s organs.
“This unique balance of speed and self-limitation, guided by specific genetic regulators, continues into infancy and may help neonates and infants fight infections while avoiding harmful inflammation during this vulnerable stage of life,” ..."
From the significance and abstract:
"Significance
During the trajectory from fetal to neonatal to infant life, naive CD8+ T cells are developmentally tuned through incompletely understood mechanisms.
Here, we report that naïve neonatal human CD8+ T cells are poised for an immediate effector switch within hours of activation, including significantly increased glycolytic capacity, proliferation and cell death, differentiation, and production of effector molecules such as TNFα.
Coupled with the distinctive transcriptomes of naïve neonatal CD8+ T cells is a unique set of transcription factors they express, which includes elevated TOX and HELIOS in both the resting and activated states. These distinctive features persist into infancy, underscoring their potential implications for shaping early-life responses to infections and vaccination while avoiding tissue immunopathology.
Abstract
Neonates and infants are distinct in their clinical and cellular responses to viral infections, with neonatal CD8+ T cells displaying innate-like characteristics and a low threshold for T cell receptor activation. However, specific molecular programs that drive these unique responses are incompletely understood, particularly in humans, and targetable pathways to modulate viral illness in this vulnerable population remain to be elucidated.
Early-life immune responses may be developmentally programmed to prioritize avoidance of tissue immunopathology, especially while maternal immunoglobulin provides passive immunity. We set out to define the unique response characteristics and transcription factor landscape of neonatal human CD8+ T cells.
Here, we report evidence that naïve neonatal human CD8+ T cells are poised for an accelerated effector switch, with elevations of killer cell lectin-like receptor G1 (KLRG1), killer cell lectin-like receptor B1 (KLRB1/CD161), Fc epsilon receptor I-gamma (FCER1G), DNAX accessory molecule-1 (DNAM1/CD226), granzymes, tumor necrosis factor alpha (TNFα), interleukin 2 (IL-2), and glycolysis compared to naïve adult CD8+ T cells.
Further, rapid proliferation and cell death occur upon activation of neonatal CD8+ T cells, with cell viability largely rescued by IL-2 or IL-7.
These features are coupled with a unique transcription factor landscape, including high expression of thymocyte selection associated high mobility group box (TOX) and HELIOS (IKZF2), and these signatures continue in postnatal life until at least 2 mo of age.
We conclude that early-life human CD8+ T cells maintain a unique transcriptional state associated with an accelerated effector switch and short-lived effector program, revealing key nodes of regulation relevant for the unique immunobiology of neonatal humans."
No comments:
Post a Comment