Patterns of engraftment in different strains of immunodeficient mice reconstituted with human peripheral blood lymphocytes

Background. Models of immunodeficient mice re constituted with a competent human immune system would represent an invaluable tool for the study of tra nsplantation immunobiology allergy, autoimmunity, and infectious diseases. Severe combined immune deficiency (scid) mice can be successfully reconstit uted with human peripheral blood lymphocytes (PBLs), but rates and levels o f engraftment are poor, New strains of mice with diverse immunodeficiencies have been recently characterized or developed, which might prove to be adv antageous for in vivo studies of human immune reactivity, Methods. We have compared rates and patterns of human PBL engraftment in fo ur available immunodeficient murine strains; scid-beige, nonobese diabetic (NOD)-scid, NOD-scid-beta2 m- and rag-. T- and B-lymphocyte engraftment, ph enotype of engrafted cells, and occurrence of graft-versus-host disease (GV HD) were studied and compared. Results. Successful engraftment of human PBL was readily obtained in the ma jority of scid-beige, NOD- scid, and NOD-scid-beta2 m- with a single i.p. a dministration of human PBLs, whereas it was seldom achieved in rag- animals . Human Ig levels were ac cordingly remarkably low in rag- recipients but, interestingly also in NOD-scid-beta2 m- mice. Engraftment was readily obser ved not only in peripheral blood but also in spleen and bone marrow of succ essfully reconstituted animals. Phenotypic analysis of engrafted human cell s showed preserved CD4/CD8 ratios and a clear skewing toward an activated p henotype, GVHD was invariably observed in successfully reconstituted animal s. Conclusions. Our data indicate that a high rate of reconstitution with huma n lymphocytes can be achieved in scid-beige, NOD-scid, and NOD-scid-beta2 m -mice. Human Ig are produced at high levels, except in NOD-scid-beta2 m-, i ncluding xenoreactive natural anti bodies. Scid-beige and NOD-scid appear t herefore better suited than NOD-scid-pa m- or rag- for analysis of human im munoreactivity in vivo. An important caveat is the invariable occurrence of GVHD that precludes long-term studies in this model system.