Models for immunodeficient mice reconstituted with a functional human immune system would be a valuable tool for the in vivo study of human immune response, notably the field of cancer biology, allergy, autoimmunity,human-specific viral infections such as HIV, and transplantation immunology. A model of SCID mice transplanted with human peripheral blood lymphocytes (hu-PBL-SCID) by a single i.p. injection was developed in the late 1980s. Reconstitution is characterized by a low rate of success, low and transient levels of chimerism in early models, but recent advances revealed that the abolishment of NK cell activity in NOD/SCID mice by antiNK antibody treatment or intercross with NK defective knock out mice results in a high degree of engraftment. Both human T and B lymphocytes were successfully developed after intra-splenic transplantation of cord blood mononuclear cells (CBMC) in novel immunodeficent mice (NOD/SCID/Jak3 deficient mice). Multicolor flowcy-tometric analysis revealed that both CD4＋and CD8＋Naive T lymphocytes (CD45RA＋CD62L＋) differentiated into the Central memory (CD45RA－CD62L＋) and Effector memory (CD45RA－CD62L－) phenotype in the mice. Naive B lymphocytes (CD19+IgD+ CD38+) also differentiated into Germinal center type(CD19＋IgD－CD38＋＋) and Memory(CD19＋IgD－CD38＋～－) phenotype. These results indicate that this system (NOD/SCID/Jak3 defi- cient mice intra-splenically xenografted with human CBMC) will be an excellent model for studies of human immuno-reaction against infectious diseases and vaccine development.
