Human BLyS facilitates engraftment of human PBL derived B cells in immunodeficient mice.

The production of fully immunologically competent humanized mice engrafted with peripheral lymphocyte populations provides a model for in vivo testing of new vaccines, the durability of immunological memory and cancer therapies. This approach is limited, however, by the failure to efficiently engraft human B lymphocytes in immunodeficient mice. We hypothesized that this deficiency was due to the failure of the murine microenvironment to support human B cell survival.

Anti-mouse CD154 antibody treatment facilitates generation of mixed xenogeneic rat hematopoietic chimerism, prevents wasting disease and prolongs xenograft survival in mice.

Background: The induction of xenogeneic hematopoietic chimerism is an attractive approach for overcoming the host response to xenografts, but establishing xenogeneic chimerism requires severe myeloablative conditioning of the recipient. The goal of this study was to determine if co-stimulation blockade would facilitate chimerism and xenograft tolerance in irradiation-conditioned concordant recipients.

Methods: Wistar Furth rat bone marrow (BM) cells were injected into irradiation-conditioned C57BL/6 mice with or without co-administration of anti-mouse CD154 monoclonal antibody (mAb).

Regulation of skin and islet allograft survival in mice treated with costimulation blockade is mediated by different CD4+ cell subsets and different mechanisms.

Background: Donor-specific transfusion (DST) and a brief course of anti-CD154 monoclonal antibody (mAb) induces permanent islet and prolonged skin allograft survival in mice. Induction of skin allograft survival requires the presence of CD4 cells and deletion of alloreactive CD8 cells. The specific roles of CD4 and CD4CD25 cells and the mechanism(s) by which they act are not fully understood.

Rejection of human islets and human HLA-A2.1 transgenic mouse islets by alloreactive human lymphocytes in immunodeficient NOD-scid and NOD-Rag1(null)Prf1(null) mice.

Immunodeficient NOD mice engrafted with human peripheral blood mononuclear cells (PBMCs) were used in two models of human islet allograft rejection. Model one: human PBMCs were engrafted into chemically diabetic NOD-scid mice bearing established subrenal human islet allografts. Inflammation and often complete islet allograft rejection were observed.

Prolonged survival of neonatal porcine islet xenografts in mice treated with a donor-specific transfusion and anti-CD154 antibody.

Background: Combined treatment with a single donor-specific transfusion (DST) and a brief course of anti-mouse CD154 monoclonal antibody (mAb) to induce co-stimulation blockade leads to long-term murine islet allograft survival. The authors hypothesized that this protocol could also induce long-term survival of neonatal porcine islet cell clusters (NPCC) in chemically diabetic immunocompetent mice and allow their differentiation into functional insulin-producing cells.

Methods: Pancreata from 1- to 3-day-old pigs were collagenase digested and cultured for 8 days.

Alloimmune injury and rejection of human skin grafts on human peripheral blood lymphocyte-reconstituted non-obese diabetic severe combined immunodeficient beta2-microglobulin-null mice.

Small animal models with the capacity to support engraftment of a functional human immune system are needed to facilitate studies of human alloimmunity. In the present investigation, non-obese diabetic (NOD) severe combined immunodeficient (scid) beta2-microglobulin-null (B2mnull) mice engrafted with human peripheral blood lymphocytes (hu-PBL-NOD-scid B2mnull mice) were used as in vivo models for studying human skin allograft rejection. Hu-PBL-NOD-scid B2mnull mice were established by injection of human spleen cells or PBLs and transplanted with full-thickness allogeneic human skin.

Regulation of human short-term repopulating cell (STRC) engraftment in NOD/SCID mice by host CD122+ cells.

Objective: NOD/SCID and NOD/SCID B2m(null) mice are used for the in vivo study of human hematopoietic stem cells (HSC). A previously unrecognized HSC in cord blood, termed short-term repopulating cell (STRC), has been identified using NOD/SCID B2m(null) mice. However, only low levels of STRC engraft in NOD/SCID mice, presumably due to their higher levels of NK cell activity.