Partial activation of neonatal CD11c+ dendritic cells and induction of adult-like CD8+ cytotoxic T cell responses by synthetic microspheres.
Neonatal cytotoxic T cell responses have only been elicited to date with immunogens or delivery systems inducing potent direct APC activation. To define the minimal activation requirements for the induction of neonatal CD8(+) cytotoxic responses, we used synthetic microspheres (MS) coated with a single CD8(+) T cell peptide from lymphocytic choriomeningitis virus (LCMV) or HIV-1. Unexpectedly, a single injection of peptide-conjugated MS without added adjuvant induced CD4-dependent Ag-specific neonatal murine cytotoxic responses with adult-like CTL precursor frequency, avidity for Ag, and frequency of IFN-gamma-secreting CD8(+) splenocytes. Neonatal CD8(+) T cell responses to MS-LCMV were elicited within 2 wk of a single immunization and, upon challenge, provided similar protection from viral replication as adult CTLs, demonstrating their in vivo competence. As previously reported, peptide-coated MS elicited no detectable activation of adult CD11c(+) dendritic cells (DC). In contrast, CTL responses were associated with a partial activation of neonatal CD11c(+) DC, reflected by the up-regulation of CD80 and CD86 expression but no concurrent changes in MHC class II or CD40 expression. However, this partial activation of neonatal DC was not sufficient to circumvent the requirement for CD4(+) T cell help. The effective induction of neonatal CD8(+) T cell responses by this minimal Ag delivery system demonstrates that neonatal CD11c(+) DC may mature sufficiently to stimulate naive CD8(+) neonatal T cells, even in the absence of strong maturation signals.
World Health Organization Collaborating Center for Neonatal Vaccinology, Department of Pathology, University of Geneva Medical School, Geneva, Switzerland.
Matthias
M
Regner
Xavier
X
Martinez
Elodie
E
Belnoue
Cheng-Ming
CM
Sun
Florence
F
Boisgerault
Paul-Henri
PH
Lambert
Claude
C
Leclerc
Claire-Anne
CA
Siegrist
D000818:Animals; D000831:Animals, Newborn; D000956:Antigens, Viral / Q000008:administration & dosage / Q000276:immunology; D039521:CD11c Antigen / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000821:virology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015497:HIV-1 / Q000276:immunology; D007114:Immunization; D008213:Lymphocyte Activation / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008863:Microspheres; D010455:Peptides / Q000276:immunology
D000956:Antigens, Viral; D039521:CD11c Antigen; D018984:Epitopes, T-Lymphocyte; D010455:Peptides