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Cytotoxic effects of rabbit anti-thymocyte globulin preparations on primary human thymic epithelial cells

Item Type:Article
Title:Cytotoxic effects of rabbit anti-thymocyte globulin preparations on primary human thymic epithelial cells
Creators Name:Kaebisch, E.M. and Cho, M.Y. and Oh, Y.S. and Olfe, L.I. and Szyska, M. and Becker, S.C. and Reinke, P. and Volk, H.D. and Gillissen, B. and Bullinger, L. and Thiel, A. and Na, I.K.
Abstract:BACKGROUND: Graft-versus-host disease (GvHD) presents a major cause for morbidity and mortality after allogeneic hematopoietic stem cell transplantation (alloHSCT). Rabbit anti-thymocyte globulin (rATG) treatment reduces the incidence of GvHD after alloHSCT. However, delayed immune reconstitution following rATG treatment, partly due to hampered thymic function, is being discussed. The present study aimed at elucidating possible cytotoxic effects of two commonly used rATG preparations on cultured human thymic stroma, especially thymic epithelial cells (TECs). METHODS: A primary thymic epithelial cell culture was established and the binding and cytotoxicity of two rATG preparations to the aforementioned cells were assessed by flow cytometry and immunofluorescence analyses. The release of several cytokines by cultured TSCs in response to rATG was analyzed via multiplex ELISA. RESULTS: Both preparations showed a comparable dose-dependent binding to TECs and exerted a similar complement-independent, dose-dependent cytotoxicity. rATG exposure further resulted in hampered secretion of IL-7, IL-15 and IL-6, cytokines being involved in thymic T cell development and proliferation. Pretreatment with keratinocyte growth factor (KGF) diminished rATG-induced cytotoxicity of TECs and restored their IL-7 and IL-15 secretion. CONCLUSIONS: Cytotoxic effects on TECs link a rATG-induced thymic damage to the delayed T cell reconstitution witnessed after rATG treatment. Our data support a combination treatment of rATG and thymus-protective strategies such as KGF in order to simultaneously offer sufficient GvHD prophylaxis and overcome delayed T cell reconstitution due to thymic damage.
Source:Transplantation
ISSN:0041-1337
Publisher:Lippincott Williams & Wilkins (U.S.A.)
Volume:103
Number:11
Page Range:2234-2244
Date:November 2019
Official Publication:https://doi.org/10.1097/TP.0000000000002799
PubMed:View item in PubMed

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