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.
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.
Belnoue
Elodie
E
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.
Fontannaz-Bozzotti
Paola
P
Grillet
Stéphane
S
Lambert
Paul-Henri
PH
Siegrist
Claire-Anne
CA
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
D000914:Antibodies, Viral