Table 3.

Models of Human Hemato-Lymphoid Cell Engraftment into Lymphopenic IL-2rγ^−/− Mice

Model Name	Description	Advantages	Applications	Limitations
Hu-PBMC-IL-2rγ−/− (Human Peripheral Blood Mononuclear Cells engrafted into lymphopenic IL-2rγ−/− mice)	Lymphopenic IL-2rγ−/− mice are injected with human peripheral mononuclear cells	A technically simple model to establish Good engraftment of effector and memory T cells.	Induced models of inflammation (e.g. sepsis, arthritis, colitis). Model of xenogeneic GVHD. Assess effector functions of T cells obtained from patients with RA, lupus, MS, diabetes or IBD Human-specific infectious diseases (HIV) Allograft tissue rejection	Only activated/memory T cells are present Lack of mature human B cells, myeloid cells, DCs, platelets and erythrocytes. Xenogeneic GVHD develops after 4–5 weeks due to human T cell reactivity against mouse MHC molecules. Limited primary immune responses.
Hu-HSC-IL-2rγ−/− (Human Hematopoietic Stem Cells engrafted into lymphopenic IL-2rγ−/− mice)	Lymphopenic IL-2rγ−/− mice are injected with CD34+ HSCs derived from fetal liver, cord blood, bone marrow, or from peripheral blood following G-CSF-mediated mobilization	Generates a naïve human immune system Development of T and B cells, APCs, myeloid cells and NK cells	Human hematopoiesis Induced models of inflammation (e.g. sepsis, arthritis, colitis) Engraft human HSCs from patients with autoimmune or chronic inflammatory diseases Human-specific infectious diseases Transplantation biology	Low rate of T cell engraftment Impaired T and B functions No mucosal immune system Lack of expression of human HLA within the thymus prevents education and development of HLA-restricted CD4+ and CD8+ T cells (DTH response is suboptimal) Only small numbers of PMNs, RBCs and megakaryocytes are present in the blood
BLT-IL-2rγ−/− (Bone marrow, Liver, Thymus engrafted into lymphopenic IL-2rγ−/− mice)	Lymphopenic IL-2rγ−/− mice are implanted with small pieces of human fetal liver and autologous thymus under the renal capsule; the mice are then injected with human CD34+ HSCs purified from the same fetal liver sample.	Human immune system engraftment is much more robust than in the Hu-SRC-NSG model. Sustained high level of T cell development; T cells are educated by the human thymus and are HLA restricted Produces human mucosal immune system	Human hematopoiesis Engraft human HSCs from patients with autoimmune or chronic inflammatory diseases Human-specific infectious diseases Transplantation biology	Surgical expertise and fetal tissue are required Responses to vaccination protocols are limited to IgM antibody production. A delayed xenogeneic GVHD (>4 months) occurs in these mice that result from the lack of negative selection against murine antigens in human thymus and/or to lack of peripheral regulation