title: Human γδ T cells are quickly reconstituted after stem-cell transplantation and show adaptive clonal expansion in response to viral infection.
abstract: To investigate how the human γδ T cell pool is shaped during ontogeny and how it is regenerated after transplantation of hematopoietic stem cells (HSCs), we applied an RNA-based next-generation sequencing approach to monitor the dynamics of the repertoires of γδ T cell antigen receptors (TCRs) before and after transplantation in a prospective cohort study. We found that repertoires of rearranged genes encoding γδ TCRs (TRG and TRD) in the peripheral blood of healthy adults were stable over time. Although a large fraction of human TRG repertoires consisted of public sequences, the TRD repertoires were private. In patients undergoing HSC transplantation, γδ T cells were quickly reconstituted; however, they had profoundly altered TCR repertoires. Notably, the clonal proliferation of individual virus-reactive γδ TCR sequences in patients with reactivation of cytomegalovirus revealed strong evidence for adaptive anti-viral γδ T cell immune responses.
authors.affiliation: Institute of Immunology, Hannover Medical School, Hannover, Germany.
authors.forename: Sarina
authors.initials: S
authors.lastname: Ravens
authors.affiliation: Institute of Immunology, Hannover Medical School, Hannover, Germany.|Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.|Integrated Research and Treatment Center Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Schultze-Florey
authors.affiliation: Institute of Immunology, Hannover Medical School, Hannover, Germany.
authors.forename: Solaiman
authors.initials: S
authors.lastname: Raha
authors.affiliation: Institute of Immunology, Hannover Medical School, Hannover, Germany.
authors.forename: Inga
authors.initials: I
authors.lastname: Sandrock
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Drenker
authors.affiliation: Institute of Immunology, Hannover Medical School, Hannover, Germany.
authors.forename: Linda
authors.initials: L
authors.lastname: Oberdörfer
authors.affiliation: Institute of Immunology, Hannover Medical School, Hannover, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Reinhardt
authors.affiliation: Institute of Immunology, Hannover Medical School, Hannover, Germany.
authors.forename: Inga
authors.initials: I
authors.lastname: Ravens
authors.affiliation: Institute of Immunology, Hannover Medical School, Hannover, Germany.|Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Maleen
authors.initials: M
authors.lastname: Beck
authors.affiliation: Genome Analytics, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Geffers
authors.affiliation: Department Obstetrics, Gynecology and Reproductive Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: Constantin
authors.initials: C
authors.lastname: von Kaisenberg
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Heuser
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Felicitas
authors.initials: F
authors.lastname: Thol
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.affiliation: Institute of Immunology, Hannover Medical School, Hannover, Germany.
authors.forename: Reinhold
authors.initials: R
authors.lastname: Förster
authors.affiliation: Institute of Immunology, Hannover Medical School, Hannover, Germany.|Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.|Integrated Research and Treatment Center Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Christian
authors.identifier: 0000-0001-7025-1735
authors.initials: C
authors.lastname: Koenecke
authors.affiliation: Institute of Immunology, Hannover Medical School, Hannover, Germany.|Integrated Research and Treatment Center Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Immo
authors.initials: I
authors.lastname: Prinz
mesh_terms: D060965:Clonal Evolution / Q000235:genetics / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D015329:Gene Rearrangement, T-Lymphocyte; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics* / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D014184:Transplantation, Homologous
chemical_list: D016692:Receptors, Antigen, T-Cell, gamma-delta