title: Regulation of the germinal center reaction by Foxp3+ follicular regulatory T cells.
abstract: Follicular helper T (T(FH)) cells participate in humoral responses providing selection signals to germinal center B cells. Recently, expression of CXCR5, PD-1, and the transcription factor Bcl-6 has allowed the identification of T(FH) cells. We found that a proportion of follicular T cells, with phenotypic characteristics of T(FH) cells and expressing Foxp3, are recruited during the course of a germinal center (GC) reaction. These Foxp3(+) cells derive from natural regulatory T cells. To establish the in vivo physiologic importance of Foxp3(+) follicular T cells, we used CXCR5-deficient Foxp3(+) cells, which do not have access to the follicular region. Adoptive cell transfers of CXCR5-deficient Foxp3(+) cells have shown that Foxp3(+) follicular T cells are important regulators of the GC reaction following immunization with a thymus-dependent Ag. Our in vivo data show that Foxp3(+) follicular T cells can limit the magnitude of the GC reaction and also the amount of secreted Ag-specific IgM, IgG1, IgG2b, and IgA. Therefore, Foxp3(+) follicular regulatory T cells appear to combine characteristics of T(FH) and regulatory T cells for the control of humoral immune responses.
authors: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, P1649-028 Lisbon, Portugal.
authors: Ivonne
authors: I
authors: Wollenberg
authors: Ana
authors: A
authors: Agua-Doce
authors: Andrea
authors: A
authors: Hernández
authors: Catarina
authors: C
authors: Almeida
authors: Vanessa G
authors: VG
authors: Oliveira
authors: Jose
authors: J
authors: Faro
authors: Luis
authors: L
authors: Graca
mesh_terms: D000818:Animals; D051858:Forkhead Transcription Factors / Q000096:biosynthesis* / Q000502:physiology; D055879:Gene Knock-In Techniques; D018858:Germinal Center / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D056724:Immunity, Humoral / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D057507:Mice, 129 Strain; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D056004:Molecular Dynamics Simulation; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse