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A common genetic variation regulates the development of Vγ9Vδ2 versus nonVγ9Vδ2 γδ T cells

par Verdebout, Isoline ;Sánchez Sánchez, Guillem ;Tafesse, Yohannes ;Dauby, Nicolas ;Cogan, Alexandra ;donner, catherine ;Papadopoulou, Maria ;Vermijlen, David
Référence 10th Internationnal gd T cell Conference (20-23/06/2023: Chapalimaud Foundation, Lisbon, Portugal)
Publication Non publié, 2023-03-31

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A common genetic variation regulates the development of Vγ9Vδ2 versus nonVγ9Vδ2 γδ T cellsIsoline Verdebout1,2,3,4, Guillem Sanchez Sanchez1,2,3,4, Yohannes Tafesse 1,2,3,4, Nicolas Dauby5, Alexandra Cogan6, Catherine Donner7, Maria Papadopoulou1,2,3,4, David Vermijlen1,2,3,41Department of Pharmacotherapy and Pharmaceutics, Université libre de Bruxelles (ULB), Brussels, Belgium2Institute of Medical Immunology, Université libre de Bruxelles (ULB), Gosselies, Belgium3ULB Center for Research in Immunology, Université libre de Bruxelles (ULB), Brussels, Belgium4 WEL Research Institute, WELBIO department, , Wavre, Belgium5 Department of Infectious Diseases, Centre Hospitalier Universitaire Saint-Pierre, Université libre de Bruxelles (ULB), Brussels, Belgium6 Department of Obstetrics and Gynecology, Centre Hospitalier Universitaire Saint-Pierre, Université libre de Bruxelles (ULB), Brussels, Belgium7 Department of Obstetrics and Gynecology, Hôpital Erasme, Université libre de Bruxelles (ULB), Brussels, BelgiumIn humans, үδ T cells can be subdivided into innate-like Vү9Vδ2 T cells and adaptive-like nonVү9Vδ2 үδ T cells, dictated by the differential usage of Vү and Vδ chains in their TCR. The prevalence of these subsets and thus the Vү and Vδ usage can be highly variable between individuals, including in antigen-inexperienced cord blood. It is not clear whether genetic factors exist that can drive this variable prevalence. Here we identified a common genetic variation driving differential prevalence of үδ T cell subsets, using multi-parameter flow cytometry and TCR/CDR3 repertoire analysis by high-throughput sequencing. This genetic variation influenced the frequencies of Vү9Vδ2 versus nonVү9Vδ2 T cells in antigen-unexperienced term-delivery cord blood. Furthermore, these differences were already present at earlier gestation times (20 weeks) of the fetus. In addition, among the nonVү9Vδ2 T cells, differential TRGV usage could be observed. Finally, in addition to differential TCR gene segment usage, the common genetic variation appeared to influence functional commitment. We are currently verifying the influence of this genetic variation on the үδ thymocyte development by investigating human thymuses ex-vivo and in artificial thymic organ cultures.