title: Donor CD4 T Cell Diversity Determines Virus Reactivation in Patients After HLA-Matched Allogeneic Stem Cell Transplantation.
abstract: Delayed reconstitution of the T cell compartment in recipients of allogeneic stem cell grafts is associated with an increase of reactivation of latent viruses. Thereby, the transplanted T cell repertoire appears to be one of the factors that affect T cell reconstitution. Therefore, we studied the T cell receptor beta (TCRβ) gene rearrangements of flow cytometry-sorted CD4(+) and CD8(+) T cells from the peripheral blood of 23 allogeneic donors before G-CSF administration and on the day of apheresis. For this purpose, TCRβ rearrangements were amplified by multiplex PCR followed by high-throughput amplicon sequencing. Overall, CD4(+) T cells displayed a significantly higher TCRβ diversity compared to CD8(+) T cells irrespective of G-CSF administration. In line, no significant impact of G-CSF treatment on the TCR Vβ repertoire usage was found. However, correlation of the donor T cell repertoire with clinical outcomes of the recipient revealed that a higher CD4(+) TCRβ diversity after G-CSF treatment is associated with lower reactivation of cytomegalovirus and Epstein-Barr virus. By contrast, no protecting correlation was observed for CD8(+) T cells. In essence, our deep TCRβ analysis identifies the importance of the CD4(+) T cell compartment for the control of latent viruses after allogeneic stem cell transplantation.
authors: Institute of Pathology, Charité - University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors: J
authors: J
authors: Ritter
authors: Institute of Pathology, Charité - University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany.|HS Diagnomics GmbH, Berlin, Germany.
authors: V
authors: V
authors: Seitz
authors: Department of Internal Medicine 5 - Hematology/Oncology, University of Erlangen, Erlangen, Germany.
authors: H
authors: H
authors: Balzer
authors: Department of Internal Medicine 5 - Hematology/Oncology, University of Erlangen, Erlangen, Germany.
authors: R
authors: R
authors: Gary
authors: Institute of Pathology, Charité - University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors: D
authors: D
authors: Lenze
authors: Department of Internal Medicine 5 - Hematology/Oncology, University of Erlangen, Erlangen, Germany.
authors: S
authors: S
authors: Moi
authors: Department of Internal Medicine 5 - Hematology/Oncology, University of Erlangen, Erlangen, Germany.
authors: S
authors: S
authors: Pasemann
authors: Institute of Pathology, Charité - University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors: A
authors: A
authors: Seegebarth
authors: Department of Internal Medicine 5 - Hematology/Oncology, University of Erlangen, Erlangen, Germany.
authors: M
authors: M
authors: Wurdack
authors: HS Diagnomics GmbH, Berlin, Germany.
authors: S
authors: S
authors: Hennig
authors: Department of Internal Medicine 5 - Hematology/Oncology, University of Erlangen, Erlangen, Germany.
authors: A
authors: A
authors: Gerbitz
authors: Institute of Pathology, Charité - University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors: M
authors: M
authors: Hummel
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D033581:Stem Cell Transplantation; D014019:Tissue Donors; D014184:Transplantation, Homologous; D014775:Virus Activation
chemical_list: D006680:HLA Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016179:Granulocyte Colony-Stimulating Factor
keywords: Bone marrow; Epstein-Barr virus (EBV); T cell biology; cytomegalovirus (CMV); donors and donation; hematopoietic stem cell transplantation; infection and infectious agents; infectious disease; molecular biology; science; translational research