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Decitabine facilitates the generation and immunosuppressive function of regulatory γδT cells derived from human peripheral blood mononuclear cells

Leukemia volume 27, pages 1580–1585 (2013)Cite this article

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Human γδT cells are innate-like immune cells, bearing specialized T-cell receptors (TCRs) that recognize nonpeptidic phosphorylated metabolites of isoprenoid biosynthesis produced by microorganisms and stressed cells. They represent only a minor fraction of T cells found in peripheral blood, which have potent functions in various aspects of immunity including infections,1 tumors,2 tissue homeostasis3 and immunoregulation.4 The diverse functions emphasize the plasticity and heterogeneity of γδT cells to influence the nature of immune response. γδT cells in different microenvironments can assume features reminiscent of classical Th1, Th2, Th17 and regulatory T cells, as well as professional antigen-presenting cells.5

Regulatory γδT cells (γδTregs) have been detected in lymphocytes infiltrating breast tumors, and in renal and skin allografts,4, 6, 7 although their detailed immunological features have not been well investigated, largely because of the lack of appropriate strategies for population expansion. Protocols for γδT cell induction and expansion have been developed by several groups, and several recent studies have focused on γδTreg identification, induction and function. Rita et al.8 reported that γδTregs, characterized by the presence of TCRγδ and a high level of forkhead/winged-helix family transcriptional repressor p3 (Foxp3) expression, existed at low but significant frequencies in humans, and could be generated in vitro from human peripheral blood mononuclear cells (hPBMCs) with immunosuppressive function. Foxp3-positive cells were also implicated in the pathogenesis of systemic lupus erythematosus.9 Thus, we hypothesized that γδTregs could be explored as an adoptive immunotherapy against graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (81170526, 81270640), Zhejiang Provincial Natural Science Foundation of China (Y2110127) and China Postdoctoral Science Foundation (2012M520202). We appreciate Novartis AG for providing ZOL and MGI Pharma for providing decitabine for this research.

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Authors and Affiliations

  1. Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China

    Y Hu, Q Cui, Y Gu, L Sheng, K Wu, J Shi, Y Tan, H Fu, L Liu, S Fu, X Yu & H Huang

  2. Department of Infectious Diseases, Peking Union Medical College Hospital, 1 Shuaifuyuan Wangfujing, Beijing, China

    Q Cui

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Hu, Y., Cui, Q., Gu, Y. et al. Decitabine facilitates the generation and immunosuppressive function of regulatory γδT cells derived from human peripheral blood mononuclear cells. Leukemia 27, 1580–1585 (2013). https://doi.org/10.1038/leu.2012.345

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