Neonatal T Follicular Helper Cells Are Lodged in a Pre-T Follicular Helper Stage Favoring Innate Over Adaptive Germinal Center Responses

Autor(es)

Mastelic-Gavillet, Beatris ^{[1, 2, 3]} ; Vono, Maria ^{[1, 2]} ; Gonzalez-Dias, Patricia ^[4] ; Ferreira, Frederico Moraes ^[5] ; Cardozo, Lucas ^[4] ; Lambert, Paul-Henri ^{[1, 2]} ; Nakaya, I, Helder ; Siegrist, Claire-Anne ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Geneva, WHO Collaborating Ctr Vaccine Immunol, Dept Pathol Immunol, Geneva - Switzerland

^[2] Univ Geneva, WHO Collaborating Ctr Vaccine Immunol, Dept Pediat, Geneva - Switzerland

^[3] Univ Lausanne, Ludwig Ctr Canc Res, Ctr Expt Therapeut, Dept Oncol, Lausanne - Switzerland

^[4] I, Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Heart Inst, Sch Med, Lab Immunol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN IMMUNOLOGY; v. 10, AUG 13 2019.
• Citações Web of Science: 0

Resumo

T follicular helper (T-fh) cells have emerged as a critical limiting factor for controlling the magnitude of neonatal germinal center (GC) reactions and primary vaccine antibody responses. We compared the functional attributes of neonatal and adult T-fh cells at the transcriptomic level and demonstrated that the T-fh cell program is well-initiated in neonates although the T-f(h) gene-expression pattern (i.e., CXCR5, IL-21, BCL6, TBK1, STAT4, ASCL2, and c-MAF) is largely underrepresented as compared to adult T-fh cells. Importantly, we identified a TH2-bias of neonatal T-fh cells, with preferential differentiation toward short-lived pre-T-fh effector cells. Remarkably, adjuvantation with CpG-ODNs redirect neonatal pre-T-fh cells toward committed GC-T-fh cells, as illustrated by increased expression of T-fh signature genes and reduced expression of TH2-related genes. (AU)

• Processo FAPESP: 12/19278-6 - Biologia de sistemas de longos RNAs não-codificadores
• Beneficiário: Helder Takashi Imoto Nakaya
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 17/50137-3 - Long noncoding RNA interplay with the host microbiome may determine mucosal influenza vaccine immunogenicity
• Beneficiário: Helder Takashi Imoto Nakaya
• Modalidade de apoio: Auxílio à Pesquisa - Regular