Environmental and T Cell–Intrinsic Factors Limit the Expansion of Neonatal Follicular T Helper Cells but May Be Circumvented by Specific Adjuvants
| Autor: | Anne-Françoise Rochat, Paul-Henri Lambert, Fabienne Tacchini-Cottier, Floriane Auderset, Elodie Belnoue, Arun T. Kamath, Béatris Mastelic, Christophe Combescure, Paola Fontannaz, Chantal Tougne, Claire-Anne Siegrist |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Aging
Adoptive cell transfer Cell Communication ddc:616.07 Cell Aging/immunology Mice 0302 clinical medicine BATF Tetanus Toxoid Germinal Center/cytology/immunology/metabolism Immunology and Allergy Cellular Senescence Aging/immunology ddc:616 0303 health sciences Cell Communication/genetics/immunology Cell Differentiation T-Lymphocytes Helper-Inducer BCL6 Adoptive Transfer medicine.anatomical_structure Cellular Microenvironment Tetanus Toxoid/administration & dosage/immunology Adjuvants Immunologic/administration & dosage/physiology T cell Cell Differentiation/genetics/immunology Immunology B-Lymphocyte Subsets CpG Islands/immunology Mice Transgenic Biology 03 medical and health sciences B-Lymphocyte Subsets/immunology/metabolism T-Lymphocytes Helper-Inducer/cytology/immunology/transplantation Adjuvants Immunologic medicine Animals B cell 030304 developmental biology Cell growth Germinal center Germinal Center Mice Inbred C57BL Cellular Microenvironment/immunology Animals Newborn Immunization CpG Islands 030215 immunology |
| Zdroj: | J Immunol Journal of immunology (Baltimore Md. : 1950) Journal of Immunology, Vol. 189, No 12 (2012) pp. 5764-72 |
| ISSN: | 0022-1767 |
| Popis: | Follicular Th (TFH) 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 CXCR5highPD-1high CD4+ TFH cells that exhibit TFH features (including Batf, Bcl6, c-Maf, ICOS, and IL-21 expression) and are able to migrate into the GCs. However, neonatal TFH cells fail to expand and to acquire a full-blown GC TFH phenotype, as reflected by a higher ratio of GC TFH/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 TFH 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 TFH 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 TFH and GC B cell neonatal responses, up to adult levels. To our knowledge, this is the first demonstration that the TFH cell development limits early life GC responses and that adjuvants/delivery systems supporting TFH differentiation may restore adultlike early life GC B cell responses. |
| Databáze: | OpenAIRE |
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