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

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 (TCR) 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, TCR rearrangements were amplified by multiplex PCR followed by high-throughput amplicon sequencing. Overall, CD4(+) T cells displayed a significantly higher TCR diversity compared to CD8(+) T cells irrespective of G-CSF administration. In line, no significant impact of G-CSF treatment on the TCR V beta repertoire usage was found. However, correlation of the donor T cell repertoire with clinical outcomes of the recipient revealed that a higher CD4(+) TCR beta 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 TCR analysis identifies the importance of the CD4(+) T cell compartment for the control of latent viruses after allogeneic stem cell transplantation.