Myeloid derived suppressor cells are present at high frequency in neonates and suppress in vitro T cell responses
Ana Gervassi1, Nicholas Lejarcegui1, Sandra Dross2
1Seattle Biomedical Research Institute, Seattle, Washington, United States of America.
Insights
Myeloid-derived suppressor cells (MDSC) are abundant in newborns, suppressing immune responses critical for vaccine efficacy. Reducing these cells may enhance infant immunity and prevent infections.
Area of Science:
- Immunology
- Neonatal Immunity
- Vaccinology
Background:
- Infant mortality from infections remains high, with many cases preventable by vaccines.
- Young infants exhibit suboptimal immune responses to infections and vaccinations.
- The underlying causes of diminished neonatal immunity are not fully understood.
Purpose of the Study:
- To investigate the role of myeloid-derived suppressor cells (MDSC) in early-life immunity.
- To determine if MDSC impede protective immunity and vaccine responsiveness in infants.
- To inform strategies for enhancing infant vaccination efficacy.
Main Methods:
- Enrolled healthy neonates, children (0-2 years), and adult controls.
- Quantified the frequency and function of MDSC in different age groups.
- Assessed MDSC suppressive capacity on T cell proliferation and cytokine production.
Main Results:
- MDSC are highly prevalent in neonates, decreasing significantly in the first months of life.
- Neonatal MDSC were identified as granulocytic MDSC (G-MDSC).
- G-MDSC potently suppressed T cell proliferation and gamma interferon production in a contact-dependent manner.
Conclusions:
- High frequencies of G-MDSC in neonates may contribute to impaired immune responses.
- Understanding G-MDSC function is crucial for improving infant vaccine efficacy.
- Targeting G-MDSC could reduce infant mortality from preventable infections.
Abstract:
Over 4 million infants die each year from infections, many of which are vaccine-preventable. Young infants respond relatively poorly to many infections and vaccines, but the basis of reduced immunity in infants is ill defined. We sought to investigate whether myeloid-derived suppressor cells (MDSC) represent one potential impediment to protective immunity in early life, which may help inform strategies for effective vaccination prior to pathogen exposure. We enrolled healthy neonates and children in the first 2 years of life along with healthy adult controls to examine the frequency and function of MDSC, a cell population able to potently suppress T cell responses. We found that MDSC, which are rarely seen in healthy adults, are present in high numbers in neonates and their frequency rapidly decreases during the first months of life. We determined that these neonatal MDSC are of granulocytic origin (G-MDSC), and suppress both CD4+ and CD8+ T cell proliferative responses in a contact-dependent manner and gamma interferon production. Understanding the role G-MDSC play in infant immunity could improve vaccine responsiveness in newborns and reduce mortality due to early-life infections.
