Infiltration Of Human Cells Research Articles

Human peripheral blood CD4 T cell-engrafted non-obese diabetic-scid IL2rγnull H2-Ab1 tm1GruTg (human leucocyte antigen D-related 4) mice: a mouse model of human allogeneic graft-versus-host disease

Graft-versus-host disease (GVHD) is a life-threatening complication of human allogeneic haematopoietic stem cell transplantation. Non-obese diabetic (NOD)-scid IL2rγ(null) (NSG) mice injected with human peripheral blood mononuclear cells (PBMC) engraft at high levels and develop a robust xenogeneic (xeno)-GVHD, which reproduces many aspects of the clinical disease. Here we show that enriched and purified human CD4 T cells engraft readily in NSG mice and mediate xeno-GVHD, although with slower kinetics compared to injection of whole PBMC. Moreover, purified human CD4 T cells engraft but do not induce a GVHD in NSG mice that lack murine MHC class II (NSG-H2-Ab1(tm1Gru), NSG-Ab°), demonstrating the importance of murine major histocompatibility complex (MHC) class II in the CD4-mediated xeno-response. Injection of purified human CD4 T cells from a DR4-negative donor into a newly developed NSG mouse strain that expresses human leucocyte antigen D-related 4 (HLA-DR4) but not murine class II (NSG-Ab° DR4) induces an allogeneic GVHD characterized by weight loss, fur loss, infiltration of human cells in skin, lung and liver and a high level of mortality. The ability of human CD4 T cells to mediate an allo-GVHD in NSG-Ab° DR4 mice suggests that this model will be useful to investigate acute allo-GVHD pathogenesis and to evaluate human specific therapies.

The IgE response in allergic asthmatic patients : the SCID mouse model

Summary Asthma is defined by three main critera : reversible airway obstruction, airway inflammation and increased airway responsiveness in response to non specific stimuli like histamine and carbachol, associated with an enhancement of the IgE production in allergic asthma. To evaluate the exact role linked to these different components of asthma, several experimental models have been proposed but results obtained are for a large part depending on the species tested and/or of the sensitization protocol used. It is the reason why we recently studied the effects of the reconstitution of SCID mice with peripheral blood mononuclear cells (PBMC) obtained from asthmatic patients sensitive to Dermatophagoides pteronyssinus. Experiments showed that humanized SCID mice have the capacity to develop a specific IgE response, especially after immunization with the related allergen. Moreover after repeated allergen exposure by inhalation, reconstituted SCID mice demonstrated an inflammatory reaction prodominant around pulmonary vessels and in small bronchi under the epithelial layer. Analysis of cell populations demonstrated the presence of CD45 RO+ Tcells, HLA-DR+ cells and some eosinophils probably of murine origin. In addition SCID mice reconstituted with PBMC of allergic asthmatics exhibited an increased bronchial hyperresponsiveness (BHR) to carbachol. So the SCID mouse model allows to identify the 3 main characteristics of allergic asthma: human IgE production, human cell infiltration and BHR, even if the characteristics of the inflammatory response are not exactly similar to that found in bronchial asthma.