Title: Subclinical GvHD in non-irradiated F1 hybrids: severe lymphoid-tissue GvHD causing prolonged immune dysfunction
Authors: Sprangers, Ben ×
Van Wijmeersch, B
Luyckx, Ariane
Sagaert, Xavier
Verbinnen, Bert
Rutgeerts, Omer
Lenaerts, Corinne
Tousseyn, Thomas
Dubois, Bénédicte
Waer, Mark
Billiau, An #
Issue Date: Apr-2011
Publisher: Scientific & Medical Division, Macmillan Press
Series Title: Bone marrow transplantation vol:46 issue:4 pages:586-596
Abstract: GvHD is an important complication of allogeneic hematopoietic SCT. Parent-in-F1 models are frequently used to study GvHD immunobiology; the characteristics of parent-in-F1 GvHD vary between strain combinations and induction protocols. Here, we observed that a high-dose challenge of non-irradiated B6DBA2F1 and B6SJLF1 recipients with C57BL/6 splenocytes left the majority of recipients clinically healthy, while inducing progressive high-grade donor T-cell chimerism. We investigated this previously undescribed pattern of parent-in-F1 T-cell alloreactivity and studied the effect of serial parental splenocyte infusions on epithelial and lymphohematopoietic tissues. The majority of recipients of 4 weekly splenocyte infusions showed long-term survival with gradual establishment of high-grade donor chimerism and without any signs of epithelial-tissue GvHD. A minority of recipients showed BM failure type of GvHD and, respectively, graft rejection. Moreover, long-term F1 chimeras showed protracted pancytopenia, and in peripheral lymphoid tissues severe lymphopenia and near-complete eradication of APCs and dysfunction in antigen-presenting capacity in remaining APC. Hematopoiesis and lymphoid tissue composition recovered only after multilineage donor chimerism had established. In conclusion, we report on a novel type of parent-in-F1 hybrid GvHD, where a cumulative high dose of C57BL/6 parental splenocytes in non-irradiated F1 mice induces subclinical but severe hematolymphoid-tissue GvHD, causing prolonged immuno-incompetence.Bone Marrow Transplantation advance online publication, 5 July 2010; doi:10.1038/bmt.2010.162.
ISSN: 0268-3369
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Translational Cell & Tissue Research
Laboratory of Experimental Transplantation
Laboratory of Clinical Bacteriology and Mycology
Research Group Experimental Neurology
Laboratory for Neuroimmunology
Experimental Laboratory Immunology
× corresponding author
# (joint) last author

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