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Impaired effector memory T-cell regulation facilitates graft versus host disease in CCR7-deficient bone marrow transplant chimeras

Item Type:Article
Title:Impaired effector memory T-cell regulation facilitates graft versus host disease in CCR7-deficient bone marrow transplant chimeras
Creators Name:de Jager, S.C. and Cante-Barrett, K. and Bot, I. and Husberg, C. and van Puijvelde, G.H. and van Santbrink, P.J. and Yndestad, A. and van den Oever, J.M. and Kuiper, J. and van Berkel, T.J. and Lipp, M. and Zwaginga, J.J. and Fibbe, W.E. and Aukrust, P. and Biessen, E.A.
Abstract:BACKGROUND: The development of graft versus host disease (GvHD) is one of the major challenges of bone marrow transplantations (BMTs). Although clinical symptoms of GvHD share many features with auto immune diseases, the underlying mechanisms remain unclear. Here, we examined the effects of hematopoietic CC-chemokine receptor (CCR)7 deficiency on the development of GvHD. METHODS: Lethally irradiated C57BL/6 mice were transplanted with bone marrow cells derived from wild-type or CCR7 C57BL/6 donor mice. RESULTS: Unlike littermate controls, CCR7 chimeras develop overt GvHD-like symptoms within 6 weeks after transplantation. Circulating CD4 and CD8 T-cell populations of CCR7 chimeras were enriched in effector memory T cells. CCR7 CD62L regulatory T-cell expansion, which typically occurs after BMT was markedly delayed in CCR7 chimeras. Furthermore, GvHD-like reactions did not occur after cotransplantation of wild-type and CCR7 bone marrow, showing that CCR7 is critically required for tolerance induction and prevention of GvHD. CONCLUSIONS: We are the first to demonstrate that lack of CCR7 results in delayed regulatory T-cell expansion. This results in insufficient control of effector memory T-cell expansion, which eventually leads to severe tissue damage. Conceivably, therapies aimed at boosting CD4 CD62L regulatory T-cell expansion after BMT could help to control GvHD.
Keywords:Graft Versus Host Disease, Chemokine Receptor, Regulatory T Cell, Memory T Cell, Animals, Mice
Source:Transplantation
ISSN:0041-1337
Publisher:Lippincott Williams & Wilkins (U.S.A.)
Volume:88
Number:5
Page Range:631-639
Date:15 September 2009
Official Publication:https://doi.org/10.1097/TP.0b013e3181b241df
PubMed:View item in PubMed

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