title: Myeloid derived suppressor cells are present at high frequency in neonates and suppress in vitro T cell responses.
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.
authors.affiliation: Seattle Biomedical Research Institute, Seattle, Washington, United States of America.
authors.forename: Ana
authors.initials: A
authors.lastname: Gervassi
authors.affiliation: Seattle Biomedical Research Institute, Seattle, Washington, United States of America.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Lejarcegui
authors.affiliation: Seattle Biomedical Research Institute, Seattle, Washington, United States of America; University of Washington Department of Global Health, Seattle, Washington, United States of America.
authors.forename: Sandra
authors.initials: S
authors.lastname: Dross
authors.affiliation: Seattle Biomedical Research Institute, Seattle, Washington, United States of America.
authors.forename: Amanda
authors.initials: A
authors.lastname: Jacobson
authors.affiliation: Seattle Biomedical Research Institute, Seattle, Washington, United States of America.
authors.forename: Grace
authors.initials: G
authors.lastname: Itaya
authors.affiliation: Division of Immunology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Elvis
authors.initials: E
authors.lastname: Kidzeru
authors.affiliation: University of British Columbia Department of Pediatrics and Child and Family Research Institute, Vancouver, Canada.
authors.forename: Soren
authors.initials: S
authors.lastname: Gantt
authors.affiliation: University of Washington Seattle Children's Hospital, Seattle, Washington, United States of America; Division of Immunology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Heather
authors.initials: H
authors.lastname: Jaspan
authors.affiliation: Seattle Biomedical Research Institute, Seattle, Washington, United States of America; University of Washington Department of Global Health, Seattle, Washington, United States of America; University of Washington Department of Medicine, Seattle, Washington, United States of America.
authors.forename: Helen
authors.initials: H
authors.lastname: Horton
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D005312:Fetal Blood / Q000166:cytology; D006098:Granulocytes / Q000166:cytology*; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000378:metabolism; D022423:Myeloid Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D007371:Interferon-gamma