Abstracts (complete list) - Wissenschaft Online

Stephan Fricke, Nadja Hilger, Manuela Ackermann, Peter Ruschpler, Lutz Uharek,
Guido Hildebrandt, Jan Matthias Braun, Frank Emmrich
Induction of xenogenic acute graft versus host disease
(aGvHD) in mice
Introduction: Acute graft versus host disease (aGvHD) is one of the major causes of
unsuccessful haematopoietic stem cell transplantation. aGvHD occurs approximately to
40%-70% in all cases and is initiated by “supravital” donor T lymphocytes which
recognize the minor or major histocompatibility antigens of a recipient. Until now, no
standard therapy for steroid refractory aGvHD is available. The development of new
therapeutic strategies (anti T cell antibodies or cellular therapeutics) and protocols
presumes suitable animal models.
Aims: The induction of graft versus host disease in a murine xenograft model by
intravenous transfer of human peripheral blood mononuclear cells in human CD4+,
murine CD4-, human DR+ triple transgenic and wild-type mice should be investigated.
Methods: Induction and severity of aGvHD in wild-type (C57/Bl/6) and triple transgenic
human CD4+, murine CD4- and human DR+ mice were investigated. Mice received
chemotherapy (cyclophosphamide and treosulfan) on day -3 to -1 before intravenous
transplantation of human PBMCs. All experimental groups were daily examined for
GvHD symptoms (severe weight loss [>10%], hunched posture, ruffled fur, reduced
mobility, tachypnoea). For determination of leucocytes by FACS and cytokines by CBA
blood of all mice were weekly collected by retro orbital bleeding. Finally, histological
examination of gut and spleen were added.
Results: By using of the triple transgenic human CD4+, murine CD4-, human DR+ mice
an acute xenogenic GvHD syndrome could be observed. In contrast, wild-type mice did
not show a GvHD syndrome (clinical scoring and histology).
Conclusion: Our results show the induction of xenogenic aGvHD in DR+ transgenic mice
while MHC-wild-type mice did not develop GvHD. In terms of application of monoclonal
antibodies as therapeutic potentiality should be considered that they have to be
produced for specific human epitopes. Therefore, the used humanised triple transgenic
mouse model is advantageously as interaction of human cell surface molecules could be
simulated.