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- Title
Subclinical GvHD in non-irradiated F1 hybrids: severe lymphoid-tissue GvHD causing prolonged immune dysfunction.
- Authors
Sprangers, B.; Van Wijmeersch, B.; Luyckx, A.; Sagaert, X.; Verbinnen, B.; Rutgeerts, O.; Lenaerts, C.; Tousseyn, T.; Dubois, B.; Waer, M.; Billiau, A. D.
- 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.
- Subjects
GRAFT versus host disease; LYMPHOID tissue; HEMATOPOIETIC stem cell transplantation; IMMUNOLOGIC diseases; BLOOD donors; EPITHELIAL cells; HEMATOPOIESIS
- Publication
Bone Marrow Transplantation, 2011, Vol 46, Issue 4, p586
- ISSN
0268-3369
- Publication type
Article
- DOI
10.1038/bmt.2010.162