Immune System Study Reveals How Infants Respond to Infections

Findings May Have Implications for Strategies to Prevent Infections and Allergies in Newborns

NEW YORK, NY (December 14, 2015) — New information about how the infant immune system works may prompt researchers and clinicians to rethink strategies for enhancing the effectiveness of newborn vaccines and preventing life-threatening allergies in children. This information is based on a study from Columbia University Medical Center (CUMC) highlighting fundamental differences between the immune systems of newborns and adults.

The study was published in today’s online edition of Nature Medicine.

Previous attempts to understand how the immune system functions in infants have drawn their conclusions from umbilical cord blood and fetal tissue. However, neither type of tissue precisely captures the moments when a newborn encounters viruses, bacteria, and other potential threats.

Such information has implications for the timing and location of newborn vaccines to enhance their protective effect. It could also help to determine whether exposure to or avoidance of a potential allergen in the first few months is optimal.

“Previously, our research team learned that, in adults, each organ has its own local immune environment that enables it to respond to the types of threat it may face,” said Donna Farber, PhD, professor of surgical sciences (in surgery and microbiology & immunology) at CUMC. “In this study, we wanted to examine how tissue immune responses are established in early life, starting from early infancy through the first two years. This would help us understand how the infant immune system ramps up as it begins to face outside threats without going into overdrive, which could harm the baby.”

The researchers examined tissue from 64 individual organ donors, including infants and adults, for whom consent was obtained through LiveOnNY, the organ procurement organization for the New York metropolitan area, and the New York-Presbyterian/Columbia pediatric liver transplant program. They measured the number of different types of T cells—a type of white blood cell made in the thymus gland that tailors the body’s response to specific pathogens—including new T cells, effector T cells that mount an initial attack against infections, and memory T cells that are generated following pathogen exposure and provide long-term immune protection.

The study found that infant tissues had more newly formed T cells than effector and memory cells throughout the body compared with adults. The highest concentrations of effector and memory cells were found exclusively in the infants’ lungs and small intestine, which are often the first point of entry for pathogens. In addition, children under age two had more regulatory T cells in their tissues and lower levels of cytokines—substances that fight infection by causing inflammation—than adults.

“These results suggest that we may be able to enhance the effectiveness of the vaccines we give during infancy and early childhood if they are targeted to the lungs and small intestine, rather than the bloodstream,” said Dr. Farber. “Furthermore, the increased number of regulatory T cells during infancy may prevent a young child’s immune system from overreacting to all newly introduced antigens. This could account for recent findings that early exposure to potential allergens, such as peanuts, may be associated with decreased allergic response compared with introducing them later in childhood.”

About the paper:

The paper is titled, “Early-life compartmentalization of human T cell differentiation and regulatory function in mucosal and lymphoid tissues.”

Additional authors included Joseph Thome, Kara Bickham, Yoshiaki Ohmura, Masaru Kubota, Nobuhide Matsuoka, Claire Gordon, Tomer Granot, Adam Griesemer, and Tomaoki Kato (CUMC) and Harvey Lerner (LiveOnNY).

The study was supported by grants from the National Institutes of health (AI100119, AI106697, and AG047003).

The researchers declare no financial or other conflicts of interest.

References

Columbia University Medical Center provides international leadership in basic, preclinical, and clinical research; medical and health sciences education; and patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Columbia University Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest faculty medical practices in the Northeast. For more information, visit cumc.columbia.edu or columbiadoctors.org.