Shared donor–recipient γδ T-cell phenotypic and repertoire features associate with cytomegalovirus reactivation after allogeneic haematopoietic stem cell transplantation

Abstract

Allogeneic haematopoietic stem cell transplantation (HSCT) is the only curative therapy for patients diagnosed with acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS). γδ+ T-cells, a rare subpopulation of T-cells with both innate and adaptive anticancer functions, have been understudied and the role of different γδ+ T-cell subsets after HSCT is unclear.

Objectives

We aimed to characterise the γδ+ T-cells reconstitution post-HSCT, investigating their association with graft-versus-host disease (GvHD) treatment and occurrence, and cytomegalovirus (CMV) reactivation.

Methods

Peripheral blood samples from AML and MDS patients and their respective donors were immunophenotyped by flow cytometry before and at several time points after HSCT. Additionally, next-generation sequencing of the TRG locus was performed to assess clonal dynamics and repertoire diversity.

Results

Early after HSCT, γδ+ T-cells showed a similar phenotype compared to pre-HSCT, and stable repertoires were observed up to 6 months post-HSCT. Patients with acute GVHD presented a higher frequency of CD8 in γδ+ T-cells, and γδ+ T-cell and subsets frequencies were not affected by anti-thymocyte globulin prophylaxis. Donor-derived Vδ2+ T-cell central memory phenotype was associated with a reduced risk of CMV reactivation in the recipient and with repertoire disturbance. Effector memory cells displaying a specific HLA-DR+ CD86+ phenotype were associated with CMV reactivation and a higher proportion of hyperexpanded clonotypes prior to transplantation.

Conclusion

Overall, Vδ1+ and Vδ2+ T-cell phenotypic profiles and γδ TCR repertoire remain stable post-HSCT. This stability is disrupted by CMV reactivation, which is potentially associated with γδ+ T-cells of donor origin and γδ TCR repertoire.