RELIEVING IMMUNOSUPPRESSION IMPROVES VΔ2+ T CELLS RECOVERY AND DECREASES EBV REACTIVATION AFTER HEMATOPOIETIC TRANSPLANTATION
Author(s): ,
Haitao Gao
Affiliations:
Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key laboratory of Hematopoietic Stem Cell Transplantation,Beijing,China
,
Jiangying Liu
Affiliations:
Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key laboratory of Hematopoietic Stem Cell Transplantation,Beijing,China
,
Lan-Ping Xu
Affiliations:
Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key laboratory of Hematopoietic Stem Cell Transplantation,Beijing,China
,
Ming Wang
Affiliations:
Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key laboratory of Hematopoietic Stem Cell Transplantation,Beijing,China
,
Ying-Jun Chang
Affiliations:
Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key laboratory of Hematopoietic Stem Cell Transplantation,Beijing,China
,
Xiao-Dong Mo
Affiliations:
Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key laboratory of Hematopoietic Stem Cell Transplantation,Beijing,China
,
Zhidong Wang
Affiliations:
Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key laboratory of Hematopoietic Stem Cell Transplantation,Beijing,China
,
Yanqun Gao
Affiliations:
Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key laboratory of Hematopoietic Stem Cell Transplantation,Beijing,China
,
Yu Wang
Affiliations:
Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key laboratory of Hematopoietic Stem Cell Transplantation,Beijing,China
,
Xiao-Hui Zhang
Affiliations:
Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key laboratory of Hematopoietic Stem Cell Transplantation,Beijing,China
Xiao-Jun Huang
Affiliations:
Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key laboratory of Hematopoietic Stem Cell Transplantation,Beijing,China
EHA Library. Gao H. Jun 15, 2019; 267160; PS1543
Haitao Gao
Haitao Gao
Contributions
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Abstract

Abstract: PS1543

Type: Poster Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00

Location: Poster area

Background
Immunosuppressive drugs have been widely used for transplantation over the last decade. Mycophenolate mofetil (MMF) and cyclosporine A (CsA) are usually used to prevent and treat graft-versus-host disease (GVHD) in the context of hematopoietic stem cell transplantation (HSCT). With the numerous studies reported the clinical efficacy of immunosuppressants, attentions for their side effects, such as opportunistic infections, are increasing. Epstein–Barr virus (EBV) reactivation and its related diseases are the common threats with high mortality after haploidentical HSCT (haploHSCT). Although the immunosuppression was associated with EBV infection after solid organ transplantation, this correlation has been less reported in the scenario of hematopoietic transplantation. We previously showed that recovery of Vδ2T cells inversely correlated to EBV reactivation after haploHSCT and Vδ2T cells isolated from haploHSCT recipients were not expanded by aminobisphosphonates stimulation. The influence of immunosuppressants on the Vδ2T cells recovery and anti-EBV cytotoxicity post-HSCT are unknown.

Aims
To investigate the impacts of immunosuppressive drugs on the Vδ2T cells expansion and function, and whether relieving the immunosuppression can improve Vδ2T cells recovery and decrease EBV reactivation in the setting of allogeneic HSCT.

Methods
Mycophenolic acid (MPA) is an active form of MMF and usually used in the in-vitro functional experiments. Pamidronate was used to trigger the expansion of Vδ2T cells in peripheral blood mononuclear cells isolated from healthy donors, with or without immunosuppressants (MPA and CsA).The activation, proliferation, functional receptor expression, cytokines production, and EBV-specific cytotoxicity of Vδ2T cellswere detected by flow cytometry. This study also included a cohort of 165 patients undergoing haploHSCT. These patients were divided into 2 groups based on the different courses of MMF administration for GVHD prophylaxis. The recoveries of T-cell subsets and incidences of EBV reactivation were statistically compared.

Results
Peripheral Vδ2T cells from healthy donors were dramatically expanded by pamidronate stimulation for 10 days, with the percentage of Vδ2T cells in total MNCs was increased from 2.8% to 89%. In contrast, MPA and CsA treatment profoundly attenuated this expansion given that Vδ2 cells levels were even lower than baseline under the same condition. The activation (expression of CD25) and IFN-γ production of Vδ2 cells were inhibited while NKG2D expression was moderately decreased by both drugs. Consistently, EBV-specific cytotoxicity of Vδ2 cells were also impaired after treatment with MPA and CsA.The recoveries of T-cell subsets were monitored in patients with different courses of MMF following haploHSCT. Recoveries of other detected T-cell subpopulations at day 30 were significantly faster in the shorter MMF group than the longer MMF group. The level of Vδ2 cells was continuously increased from 30 to 90 days post-haploHSCT after reducing the course of MMF, accompanied with a decreased incidence of EBV reactivation. Day-30 Vδ2 levels remained an independent factor for EBV reactivation in patients with different MMF durations.

Conclusion
Reliving the suppression of MMF and CsA is favorable to anti-EBV immunity probably through recovering Vδ2 cells expansion and function. These findings will help improve the outcome of hematopoietic transplant.

Session topic: 22. Stem cell transplantation - Clinical

Keyword(s): Epstein barr virus, Hematopoietic cell transplantation, Immune reconstitution, Immunosuppressive therapy

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