Donor CD4 T Cell Diversity Determines Virus Reactivation in Patients After HLA-Matched Allogeneic Stem Cell Transplantation

Am J Transplant. 2015 Aug;15(8):2170-9. doi: 10.1111/ajt.13241. Epub 2015 Apr 14.


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.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adult
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Case-Control Studies
  • Female
  • Granulocyte Colony-Stimulating Factor / administration & dosage
  • HLA Antigens / immunology*
  • Humans
  • Male
  • Middle Aged
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • Stem Cell Transplantation*
  • Tissue Donors*
  • Transplantation, Homologous
  • Virus Activation*


  • HLA Antigens
  • Receptors, Antigen, T-Cell, alpha-beta
  • Granulocyte Colony-Stimulating Factor