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γδ T cells perform antitumor and antiviral effector functions and are involved in both innate and adaptive immunity. Vδ2 +  T cells represent the predominant γδ T subset in the peripheral blood of healthy subjects. Vδ2 +  T cells can be selectively activated and expanded by phosphoantigens (pAgs). Dendritic cells (DCs), as potent antigen-presenting cells, are capable of mediating pAgs–triggered Vδ2 +  T cells expansion. However, the association between DCs and Vδ2 +  T cell recovery in the context of hematopoietic stem cell transplantation (HSCT) remains unclear. We previously demonstrated that the recovery of Vδ2 +  T cells was hampered and inversely correlated with Epstein-Barr virus (EBV) reactivation in patients undergoing haploidentical HSCT (haploHSCT). Whether Vδ2 +  T cells from haploHSCT recipients can be expanded by stimulation with aminobisphosphonates or pAg–presenting DCs is of particular interest. Herein, we showed that Vδ2 +  T cells recovered after haploHSCT failed to expand after  ex-vivo  stimulation with pamidronate. In addition, we found that the recovery of DC subsets was significantly decreased, and the concentration of myeloid DCs (mDCs) correlated significantly with Vδ2 +  T cell recovery in the setting of allogeneic HSCT. Furthermore, coculture of peripheral lymphocytes from recipients with monocyte-derived and pamidronate-pretreated autologous or allogeneic DCs induced the successful expansion of Vδ2 +  T cells. Of note, allogeneic DCs from third-party donors stimulated a significantly higher efficiency of Vδ2 +  T cell expansion than autologous DCs. More importantly, the memory features were well-retained and the cytotoxic cytokines-production capacity was significantly enhanced in the expanded Vδ2 +  T cells. Taken together, these results suggest that the frequency and function of DCs are critical for the recovery of Vδ2 +  T cells after allogeneic HSCT. The fact that vigorous expansions of Vδ2 +  T cells were induced by phosphoantigen-pretreated DCs, especially by allogeneic third-party DCs, provides additional options for the development of individualized immunotherapy strategies that utilize the anti-viral and anti-leukemic effects of γδ T cells in the context of hematopoietic transplantation.

Dendritic Cells Are Critical for the Activation and Expansion of Vδ2+ T Cells After Allogeneic Hematopoietic Transplantation