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

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Published in The Journal of immunology. 2012, vol. 189, no. 12, p. 5764-72
Abstract 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.
Keywords Adjuvants, Immunologic/administration & dosage/physiologyAdoptive TransferAging/immunologyAnimalsAnimals, NewbornB-Lymphocyte Subsets/immunology/metabolismCell Aging/immunologyCell Communication/genetics/immunologyCell Differentiation/genetics/immunologyCellular Microenvironment/immunologyCpG Islands/immunologyGerminal Center/cytology/immunology/metabolismImmunizationMiceMice, Inbred C57BLMice, TransgenicT-Lymphocytes, Helper-Inducer/cytology/immunology/transplantationTetanus Toxoid/administration & dosage/immunology
PMID: 23162125
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Research groups Centre de Vaccinologie et d'Immunologie néonatale (177)
Epidémiologie clinique (115)
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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. 5764-72. doi: 10.4049/jimmunol.1201143 https://archive-ouverte.unige.ch/unige:31487

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Deposited on : 2013-11-29

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