title: Protracted course of lymphocytic choriomeningitis virus WE infection in early life: induction but limited expansion of CD8+ effector T cells and absence of memory CD8+ T cells.
abstract: Viral infections in human infants frequently follow a protracted course, with higher viral loads and delayed viral clearance compared to viral infections in older children. To identify the mechanisms responsible for this protracted pattern of infection, we developed an infant infection murine model using the well-characterized lymphocytic choriomeningitis virus (LCMV) WE strain in 2-week-old BALB/c mice. In contrast to adult mice, in which viral clearance occurred as expected 8 days after infection, LCMV titers persisted for several weeks after infection of infant mice. LCMV-specific effector CD8(+) T cells were elicited in infant mice and fully functional on day 7 but rapidly waned and could not be recovered from day 12 onwards. We show here that this results from the failure of LCMV-specific CD8(+) T cells to expand and the absence of protective LCMV-specific memory CD8(+) T cells. Under these early life conditions, viral control and clearance are eventually achieved only through LCMV-specific B cells that contribute to protect infant mice from early death or chronic infection.
authors.affiliation: World Health Organization Collaborating Center for Vaccinology and Neonatal Immunology, Department of Pathology-Immunology, University of Geneva, Centre Médical Universitaire, Rue Michel Servet 1, 1211 Geneva 4, Switzerland.
authors.forename: Elodie
authors.initials: E
authors.lastname: Belnoue
authors.forename: Paola
authors.initials: P
authors.lastname: Fontannaz-Bozzotti
authors.forename: Stéphane
authors.initials: S
authors.lastname: Grillet
authors.forename: Paul-Henri
authors.initials: PH
authors.lastname: Lambert
authors.forename: Claire-Anne
authors.initials: CA
authors.lastname: Siegrist
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000831:Animals, Newborn; D000914:Antibodies, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division; D007156:Immunologic Memory; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology / Q000302:isolation & purification*; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests
chemical_list: D000914:Antibodies, Viral