Scientific article

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

Published inThe Journal of immunology, vol. 189, no. 12, p. 5764-5772
Publication date2012

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.

  • Adjuvants, Immunologic/administration & dosage/physiology
  • Adoptive Transfer
  • Aging/immunology
  • Animals
  • Animals, Newborn
  • B-Lymphocyte Subsets/immunology/metabolism
  • Cell Aging/immunology
  • Cell Communication/genetics/immunology
  • Cell Differentiation/genetics/immunology
  • Cellular Microenvironment/immunology
  • CpG Islands/immunology
  • Germinal Center/cytology/immunology/metabolism
  • Immunization
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • T-Lymphocytes, Helper-Inducer/cytology/immunology/transplantation
  • Tetanus Toxoid/administration & dosage/immunology
Citation (ISO format)
MASTELIC-GAVILLET, Beatris et al. Environmental and T cell-intrinsic factors limit the expansion of neonatal follicular T helper cells but may be circumvented by specific adjuvants. In: The Journal of immunology, 2012, vol. 189, n° 12, p. 5764–5772. doi: 10.4049/jimmunol.1201143
Main files (1)
Article (Published version)
ISSN of the journal0022-1767

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