title: T cell receptor repertoires after adoptive transfer of expanded allogeneic regulatory T cells.
abstract: Regulatory T cell (Treg) therapy has been exploited in autoimmune disease, solid organ transplantation and in efforts to prevent or treat graft-versus-host disease (GVHD). However, our knowledge on the in-vivo persistence of transfused Tregis limited. Whether Tregtransfusion leads to notable changes in the overall Tregrepertoire or whether longevity of Tregin the periphery is restricted to certain clones is unknown. Here we use T cell receptor alpha chain sequencing (TCR-α-NGS) to monitor changes in the repertoire of Tregupon polyclonal expansion and after subsequent adoptive transfer. We applied TCR-α-NGS to samples from two patients with chronic GVHD who received comparable doses of stem cell donor derived expanded Treg. We found that in-vitro polyclonal expansion led to notable repertoire changes in vitro and that Tregcell therapy altered the peripheral Tregrepertoire considerably towards that of the infused cell product, to different degrees, in each patient. Clonal changes in the peripheral blood were transient and correlated well with the clinical parameters. We suggest that T cell clonotype analyses using TCR sequencing should be considered as a means to monitor longevity and fate of adoptively transferred T cells.
authors: DFG-Center for Regenerative Therapies Dresden, Dresden, Germany.|Internal Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany.
authors: A
authors: A
authors: Theil
authors: DFG-Center for Regenerative Therapies Dresden, Dresden, Germany.
authors: C
authors: C
authors: Wilhelm
authors: Institute for Medical Informatics and Biometry, Faculty of Medicine Carl Gustav Carus, Dresden, Germany.
authors: M
authors: M
authors: Kuhn
authors: Deep Sequencing Group, Biotechnology Center, Technische Universität Dresden, Dresden, Germany.
authors: A
authors: A
authors: Petzold
authors: Internal Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany.
authors: S
authors: S
authors: Tuve
authors: Internal Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany.
authors: U
authors: U
authors: Oelschlägel
authors: Deep Sequencing Group, Biotechnology Center, Technische Universität Dresden, Dresden, Germany.
authors: A
authors: A
authors: Dahl
authors: Internal Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany.
authors: M
authors: M
authors: Bornhäuser
authors: DFG-Center for Regenerative Therapies Dresden, Dresden, Germany.
authors: E
authors: E
authors: Bonifacio
authors: DFG-Center for Regenerative Therapies Dresden, Dresden, Germany.
authors: A
authors: A
authors: Eugster
mesh_terms: D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D006086:Graft vs Host Disease / Q000175:diagnosis* / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology* / Q000637:transplantation; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta
keywords: T cell receptor repertoire; cell tracking; next generation sequencing; regulatory T cell therapy