A lifelong journey: Researchers create first single-cell atlas of the human immune system from infancy to age 105

The human immune system is constantly changing. It learns from infections, responds to vaccines, and adapts throughout life. Yet until now, we lacked a comprehensive map of how the immune system develops from the earliest months of life through centenarians. A team led by Duygu Ucar, professor and Florine Deschenes Roux Chair for Genomics and Computational Biology at The Jackson Laboratory for Genomic Medicine in Farmington, Conn., and Djamel Nehar-Belaid, now an assistant professor at Emory University, created a new map of immune cells across the human lifespan and found that infants do not simply have an immature immune system; they have a fundamentally different one.   

The study profiled more than one million immune cells from 167 healthy individuals ranging from two months to 105 years of age, revealing how the immune system develops, matures, and remodels throughout life. While previous immune atlases have focused on either children or adults, none captured both ends of the lifespan in a single study.

The research, published in Nature Communications, was conducted at JAX, in close collaboration with Octavio Ramilo from St. Jude Children's Research Hospital and George Kushel from UConn Health to generate one of the most comprehensive single-cell atlases of the healthy human immune system ever assembled.

“One of the biggest surprises was finding that healthy infants already maintain a baseline antiviral program,” said Ucar. “Rather than waiting until an infection occurs, parts of the infant immune system appear to be naturally poised to respond. Understanding how this protective state is established and maintained could ultimately help us design better vaccines and therapies for early life.”

Infancy emerges as the most dynamic stage of immune development

The researchers found that the first months of life are characterized by unique immune cell populations and molecular programs rarely seen later in life. Among the most notable was the expansion of SOX4-positive naïve T cells, a previously underappreciated population that may play an important role in establishing adaptive immunity during early life.

The team also discovered that healthy infants maintain naturally elevated expression of interferon-stimulated genes (ISGs) across several immune cell types—even in the absence of infection or recent vaccination. Interferons are part of the body's first line of defense against viruses, suggesting that infants may exist in a unique “ready-to-respond” immune state while their adaptive immune system is still developing.

The researchers also observed that infants possess a distinct balance of immune cells, including expanded plasmacytoid dendritic cells (pDCs), specialized antiviral cells that produce type I interferons, further supporting the idea that early-life immunity follows its own developmental trajectory.

“Infants experience the highest burden of many infectious diseases, and their immune responses to vaccines are often different from those of older children and adults,” said Nehar-Belaid, first author of the study. “Yet we still know surprisingly little about the molecular programs that shape immunity during this critical period of life.”

“This atlas provides a foundation for asking those questions,” he added. “And my laboratory will build on these discoveries to understand how early-life immune programs develop and how they can be harnessed to improve vaccines and protect infants from infectious diseases.”

The immune system follows different trajectories throughout life

The atlas also revealed that immune aging is far more complex than a simple decline. Some immune cells steadily decrease with age, while others expand, and some follow unexpected patterns. Two specialized T-cell populations (MAIT cells and γδ T cells) showed a distinctive “rise-and-fall” trajectory. Their numbers increased throughout childhood, peaked during young adulthood, and gradually declined with aging, highlighting that different parts of the immune system mature and age on their own timelines.

The researchers also found that conventional CD8⁺ T cells undergo profound remodeling with age, gradually shifting away from naïve cells toward highly differentiated immune cells associated with lifelong immune experience.

Individuals over 85 years of age displayed additional immune adaptations, suggesting that healthy longevity is accompanied by continued immune remodeling rather than simply immune decline.

A resource for the entire research community

Beyond its biological discoveries, the atlas provides an open reference for researchers studying infectious diseases, autoimmune disorders, cancer, vaccine responses, and aging.

“Whether we’re studying childhood infections, autoimmune diseases, vaccine responses, or healthy aging, the first question is always the same: What does healthy immunity look like?” said Ucar. “This atlas gives researchers that baseline. We hope it becomes a foundational resource that helps accelerate discoveries across many areas of medicine.”

JAX media contact: Patrick Skahill, [email protected], 860-839-3309.

Learn more about The Jackson Laboratory.

Citation: Nehar-Belaid, D. et al. Single-cell map of the healthy human immune system across the lifespan reveals unique infant immune signatures. Nature Communications. 2026. DOI: 10.1038/s41467-026-73729-2