title: Effector Vγ9Vδ2 T cells dominate the human fetal γδ T-cell repertoire.
abstract: γδ T cells are unconventional T cells recognizing antigens via their γδ T-cell receptor (TCR) in a way that is fundamentally different from conventional αβ T cells. γδ T cells usually are divided into subsets according the type of Vγ and/or Vδ chain they express in their TCR. T cells expressing the TCR containing the γ-chain variable region 9 and the δ-chain variable region 2 (Vγ9Vδ2 T cells) are the predominant γδ T-cell subset in human adult peripheral blood. The current thought is that this predominance is the result of the postnatal expansion of cells expressing particular complementary-determining region 3 (CDR3) in response to encounters with microbes, especially those generating phosphoantigens derived from the 2-C-methyl-d-erythritol 4-phosphate pathway of isoprenoid synthesis. However, here we show that, rather than requiring postnatal microbial exposure, Vγ9Vδ2 T cells are the predominant blood subset in the second-trimester fetus, whereas Vδ1(+) and Vδ3(+) γδ T cells are present only at low frequencies at this gestational time. Fetal blood Vγ9Vδ2 T cells are phosphoantigen responsive and display very limited diversity in the CDR3 of the Vγ9 chain gene, where a germline-encoded sequence accounts for >50% of all sequences, in association with a prototypic CDR3δ2. Furthermore, these fetal blood Vγ9Vδ2 T cells are functionally preprogrammed (e.g., IFN-γ and granzymes-A/K), with properties of rapidly activatable innatelike T cells. Thus, enrichment for phosphoantigen-responsive effector T cells has occurred within the fetus before postnatal microbial exposure. These various characteristics have been linked in the mouse to the action of selecting elements and would establish a much stronger parallel between human and murine γδ T cells than is usually articulated.
authors.affiliation: Institute for Medical Immunology, Université Libre de Bruxelles (ULB), 6041 Gosselies, Belgium;
authors.forename: Tanya
authors.initials: T
authors.lastname: Dimova
authors.affiliation: Institute for Medical Immunology, Université Libre de Bruxelles (ULB), 6041 Gosselies, Belgium;
authors.forename: Margreet
authors.initials: M
authors.lastname: Brouwer
authors.affiliation: Department of Obstetrics and Gynecology, Hôpital Erasme, 1070 Brussels, Belgium;
authors.forename: Françoise
authors.initials: F
authors.lastname: Gosselin
authors.affiliation: ImmuneHealth, 6041 Gosselies, Belgium; and.
authors.forename: Joël
authors.initials: J
authors.lastname: Tassignon
authors.affiliation: Institute for Medical Immunology, Université Libre de Bruxelles (ULB), 6041 Gosselies, Belgium;
authors.forename: Oberdan
authors.initials: O
authors.lastname: Leo
authors.affiliation: Department of Obstetrics and Gynecology, Hôpital Erasme, 1070 Brussels, Belgium;
authors.forename: Catherine
authors.initials: C
authors.lastname: Donner
authors.affiliation: Institute for Medical Immunology, Université Libre de Bruxelles (ULB), 6041 Gosselies, Belgium;
authors.forename: Arnaud
authors.initials: A
authors.lastname: Marchant
authors.affiliation: Institute for Medical Immunology, Université Libre de Bruxelles (ULB), 6041 Gosselies, Belgium; Faculty of Pharmacy, Université Libre de Bruxelles (ULB), 1050 Brussels, Belgium dvermijl@ulb.ac.be.
authors.forename: David
authors.initials: D
authors.lastname: Vermijlen
mesh_terms: D000818:Animals; D017931:DNA Primers / Q000235:genetics; D005333:Fetus / Q000276:immunology*; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D007107:Immune System / Q000254:growth & development*; D051379:Mice; D046228:Microarray Analysis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D017422:Sequence Analysis, DNA; D018709:Statistics, Nonparametric; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
chemical_list: D017931:DNA Primers; D016692:Receptors, Antigen, T-Cell, gamma-delta
keywords: Vγ9Vδ2; fetus; gammadelta; human; neonate