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

Mastelic-Gavillet, Beatris; Kamath, Arun; Fontannaz, Paola; Tougne, Chantal; Rochat, Anne-Françoise; Belnoue, Elodie; Combescure, Christophe; Auderset, Floriane; Lambert, Paul Henri; Tacchini-Cottier, Fabienne; Siegrist, Claire-Anne

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Title		Environmental and T cell-intrinsic factors limit the expansion of neonatal follicular T helper cells but may be circumvented by specific adjuvants
Authors		Mastelic-Gavillet, Beatris Kamath, Arun Fontannaz, Paola Tougne, Chantal Rochat, Anne-Françoise Belnoue, Elodie Combescure, Christophe Auderset, Floriane Lambert, Paul Henri Tacchini-Cottier, Fabienne Siegrist, Claire-Anne show all authors [1 - 11]
Published in		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/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
Identifiers		DOI: 10.4049/jimmunol.1201143 PMID: 23162125
Full text		Article (Published version) (1.3 MB) - Limited access to UNIGE
Structures		Faculté de médecine / Section de médecine clinique / Département de médecine interne des spécialités Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie Faculté de médecine / Section de médecine clinique / Département de pédiatrie
Research groups		Epidémiologie clinique (115) Centre de Vaccinologie et d'Immunologie néonatale (177)
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: Journal of Immunology, 2012, vol. 189, n° 12, p. 5764-72. https://archive-ouverte.unige.ch/unige:31487