Environmental and T cell-intrinsic factors limit the expansion of neonatal follicular T helper cells but may be circumvented by specific adjuvants.

Détails

ID Serval
serval:BIB_FA96F491398B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Environmental and T cell-intrinsic factors limit the expansion of neonatal follicular T helper cells but may be circumvented by specific adjuvants.
Périodique
Journal of Immunology
Auteur(s)
Mastelic B., Kamath A.T., Fontannaz P., Tougne C., Rochat A.F., Belnoue E., Combescure C., Auderset F., Lambert P.H., Tacchini-Cottier F., Siegrist C.A.
ISSN
1550-6606 (Electronic)
ISSN-L
0022-1767
Statut éditorial
Publié
Date de publication
2012
Volume
189
Numéro
12
Pages
5764-5772
Langue
anglais
Résumé
Follicular Th (T(FH)) cells have emerged as a new Th subset providing help to B cells and supporting their differentiation into long-lived plasma cells or memory B cells. Their differentiation had not yet been investigated following neonatal immunization, which elicits delayed and limited germinal center (GC) responses. We demonstrate that neonatal immunization induces CXCR5(high)PD-1(high) CD4(+) T(FH) cells that exhibit T(FH) features (including Batf, Bcl6, c-Maf, ICOS, and IL-21 expression) and are able to migrate into the GCs. However, neonatal T(FH) cells fail to expand and to acquire a full-blown GC T(FH) phenotype, as reflected by a higher ratio of GC T(FH)/non-GC CD4(+) T cells in immunized adults than neonates (3.8 × 10(-3) versus 2.2 × 10(-3), p = 0.01). Following the adoptive transfer of naive adult OT-II CD4(+) T cells, OT-II T(FH) cells expand in the vaccine-draining lymph nodes of immunized adult but not infant recipients, whereas naive 2-wk-old CD4(+) OT-II cells failed to expand in adult hosts, reflecting the influence of both environmental and T cell-intrinsic factors. Postponing immunization to later in life increases the number of T(FH) cells in a stepwise manner, in direct correlation with the numbers of GC B cells and plasma cells elicited. Remarkably, adjuvantation with CpG oligonucleotides markedly increased GC T(FH) and GC B cell neonatal responses, up to adult levels. To our knowledge, this is the first demonstration that the T(FH) cell development limits early life GC responses and that adjuvants/delivery systems supporting T(FH) differentiation may restore adultlike early life GC B cell responses.
Pubmed
Web of science
Open Access
Oui
Création de la notice
19/12/2012 11:55
Dernière modification de la notice
09/05/2019 3:48
Données d'usage