γδ T cell characterisation in the long term after haematopoietic stem cell transplantation and its impact on CMV control and cGVHD severity.

Objectives: The clinical outcome after allogeneic haematopoietic stem cell transplantation (aHCT) relies greatly on the efficient recovery of T cells. Several studies have investigated the short-term γδ T cell reconstitution and their role in clinical outcomes following haematopoietic stem cell transplantation. Nevertheless, their long-term characteristics and impact have remained largely unknown.

Methods: We analysed γδ T cells from 20 recipient/donor pairs at phenotypic, clonotypic and functional levels to assess their reconstitution ≥ 8 years (median 18 years) post-transplantation using high-parameter flow cytometry and next-generation sequencing of the TCR γ-chain.

Results: γδ T cells displayed comparable phenotypic characteristics between recipients and matching donors. The Vδ2 subset showed a more activated phenotype and cytokine production, while the Vδ1 and non-Vδ2 T cells maintained long-term CMV control. TCR γ-chain composition in long-term survivors was largely restored, with no significant differences in gene segment usage or diversity. A small cohort of recipients with severe chronic graft-versus-host disease (GVHD) showed overrepresented donor-derived private clonotypes. Furthermore, we also found elevated HLA-DRVδ1 T cells in recipients with severe chronic GVHD.

Conclusion: Overall, γδ T cells reconstitute with a normalised repertoire, high functional capacity and sustained CMV control ability. An increased proportion of activated Vδ1 T cells correlates with chronic GVHD severity, indicating a potential therapeutic target.