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

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Abstract
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‐DR+Vδ1+ 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.
Funding Information
  • Vetenskapsrådet
  • Cancerfonden

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