Human Immune System Models	Common Abbreviati on	Establishment of Model	Advantages	Limitations
Human Peripheral Blood Lymphocyte engrafted immunodeficient (SCID) mouse	Hu-PBL-SCID	Injection of peripheral lymphoid cells	Easy to establish Good T cell engraftment Engrafts an effector/memory T cell immune population Model of xeno-graft- versus-host disease (GVHD)	Predominately T cells engraft, B and myeloid cells do not engraft well All T cells engrafted are activated Limited window for experimentation due to GVHD Hard to generate primary immune responses Xeno-GVHD confounds induced human immune responses Host APCs do not express HLA and do not interact with engrafted T cells
Human Scid-Repopulating Cell SCID	Hu-SRC-SCID	Injection of newborn or adult mice with hematopoietic stem cells derived from fetal liver, cord blood, bone marrow or from granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood	Development of multiple lineages of hematopoietic cells, ncluding T and B cells, PCs, myeloid cells and NK cells. Engraftment of newborns leads to higher levels of CD3 T cells7 Generates a naïve human immune system	Human T cells are educated onmouse thymic epithelium and areH2-restricted, not HLA-restricted124 Human-derived polymorphonuclear leukocytes, red blood cells (RBCs),and megakaryocytes are present in bone marrow but only low levels circulate in the blood
SCID-Human	SCID-Hu	Co-implantation of human fetal liver and thymus under the renal capsule	Human T cells are educated on autologous thymic epithelium and are LA-restricted Robust thymus and T cell development is observed in the thymus Excellent model for study of HIV	Low levels of haematopoietic cell lineages other than T cells are generated Low levels of haematopoietic engraftment in bone marrow and peripheral tissues Poor human immune system function
Bone marrow, Liver, Thymus	BLT	Human fetal liver and autologous thymus fragments are co-implanted under the renal capsule of an immunodeficient mouse, and following preconditioning human HSCs isolated from the same fetal liver are then injected intravenously to engraft the bone marrow48	Complete human immune system engrafted, including antigen-presentingcells T cells are HLA- restricted Higher levels of total human haematopoietic cell engraftment than in Hu-SRC-SCID model Only model that leads to the generation of a mucosal human immune system	Technical and surgical expertise required for establishment of the model system Fetal tissue availability may be limiting Long-term BLT mice begin to display a “wasting” like diseasewith multi-organ infiltration and inflammation and eventual death Immune responses although present are weak and vaccinations for viruses are not protective Predominately IgM antibody responses to immunization or virus infection with little IgG antibodygenerated