| Title | Dendritic Cells Are Critical for the Activation and Expansion of V delta 2(+) T Cells After Allogeneic Hematopoietic Transplantation |
| Authors | Wang, Xiaoyu Liu, Jiangying Gao, Haitao Mo, Xiao-Dong Han, Tingting Xu, Lan-Ping Zhang, Xiao-Hui Huang, Xiao-Jun |
| Affiliation | Peking Univ, Peoples Hosp, Inst Hematol, Beijing Key Lab Hematopoiet Stem Cell Transplanta, Beijing, Peoples R China. Beijing Hightrust Diagnost Co Ltd, Beijing, Peoples R China. |
| Keywords | hematopoietic stem cell transplantation immune reconstitution gamma delta T cells dendritic cells aminobisphosphonate BREAST-CANCER PATIENTS ZOLEDRONIC ACID ANTITHYMOCYTE GLOBULIN MULTIPLE-MYELOMA ACUTE-LEUKEMIA FREE SURVIVAL CROSS-TALK IMMUNOTHERAPY RECONSTITUTION STIMULATION |
| Issue Date | 2018 |
| Publisher | FRONTIERS IN IMMUNOLOGY |
| Citation | FRONTIERS IN IMMUNOLOGY. 2018, 9. |
| Abstract | gamma delta T cells perform antitumor and antiviral effector functions and are involved in both innate and adaptive immunity. V delta(2+) T cells represent the predominant gamma delta T subset in the peripheral blood of healthy subjects. V delta(2+) 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 V delta(2+) T cells expansion. However, the association between DCs and V delta(2+) T cell recovery in the context of hematopoietic stemcell transplantation (HSCT) remains unclear. We previously demonstrated that the recovery of V delta(2+) T cells was hampered and inversely correlated with Epstein-Barr virus (EBV) reactivation in patients undergoing haploidentical HSCT (haploHSCT). Whether V delta(2+) T cells from haploHSCT recipients can be expanded by stimulation with aminobisphosphonates or pAg-presenting DCs is of particular interest. Herein, we showed that V delta(2+) 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 V delta(2+) 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 V delta(2+) T cells. Of note, allogeneic DCs fromthird-party donors stimulated a significantly higher efficiency of V delta(2+) 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 V delta(2+) T cells. Taken together, these results suggest that the frequency and function of DCs are critical for the recovery of V delta(2+) T cells after allogeneic HSCT. The fact that vigorous expansions of V delta(2+) 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 gamma delta T cells in the context of hematopoietic transplantation. |
| URI | http://hdl.handle.net/20.500.11897/568216 |
| ISSN | 1664-3224 |
| DOI | 10.3389/fimmu.2018.02528 |
| Indexed | SCI(E) Medline |
| Appears in Collections: | 人民医院 |
