Graft-versus-host disease is associated with skewed γδ T-cell clonality after umbilical cord blood transplantation in children with nonmalignant diseases

Background aims: The γδ T-cells (GDT) are a subpopulation of lymphocytes expressing a distinct T-cell receptor coded by the TRG and TRD genes. GDTs may have immunoregulatory function after stem cell transplantation (SCT), but the relationship between GDT clonality and acute graft-versus-host disease (aGVHD) is not known.

Methods: We prospectively studied spectratype complex complexity of TCR Vγ (γ) and TCR Vδ (δ) pre-SCT and at approximately day 100 and day 180 post-SCT in a cohort of immunocompetent children receiving allogeneic umbilical cord blood SCT for nonmalignant diseases, with identical reduced-intensity conditioning and aGVHD prophylaxis.

Results: We studied 13 children undergoing SCT at a median age of 0.9 years (total range 0.4-16.6). In those with grade 0-1 aGVHD (N = 10), the spectratype complexity of most γ and δ genes was not significantly different from baseline at day 100 or day 180 post-SCT, and there was balanced expression of genes at the γ and δ loci. In those with grade 3 aGVHD (N = 3), spectratype complexity was significantly below baseline at day 100 and day 180, and there was relative overexpression of δ2. CD3+ cell counts were also lower in participants with grade 3 aGVHD.

Conclusions: Recovery of a polyclonal GDT repertoire is an early part of immunological recovery after SCT. γ and δ gene expression is balanced in young children before and after SCT. Severe aGVHD is associated with GDT oligoclonality post-SCT and with skewed expression of δ2, which has not been previously reported. This association may reflect aGVHD therapy or aGVHD-associated immune dysregulation. Further studies of GDT clonality during the early post-SCT period may establish whether abnormal GDT spectratype precedes the clinical manifestations of aGVHD.