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.
Diabetes-Mellitus, Gene-Deletion, Genes-RAG-1, Graft-Rejection, Graft-vs-Host-Disease, HLA-A2-Antigen, Humans, Islets-of-Langerhans, Islets-of-Langerhans-Transplantation, Lymphocytes, Membrane-Glycoproteins, Mice, Mice-Inbred-NOD, Mice-Knockout, Mice-Transgenic, Research-Support-Non-U, S, -Gov't, Research-Support-U, S, -Gov't-P, H, S, Severe-Combined-Immunodeficiency, Spleen, Transplantation-Homologous
Clin Immunol 2004 Sep; 112(3):273-83.
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. Model 2 incorporated three key advances. First, we developed a new immunodeficient recipient, NOD-RagI(null)Prf1(null) mice. Second, graft-lymphocyte interactions were optimized by intrasplenic co-transplantation of islets and human PBMC. Third, NOD-scid islets expressing human HLA-A2.1 were used as allograft targets. Diabetic NOD-RagI(null)Prf1(null) recipients of HLA-A2.1 transgenic mouse islets, alone or co-engrafted with HLA-A2-positive human PBMC, exhibited durable graft survival and euglycemia. Contrastingly, co-transplantation with HLA-A2-negative human PBMC led to islet graft rejection without evidence of graft-vs.-host disease (GVHD). We propose that diabetic NOD-RagI(null)Prf1(null) mice co-engrafted with HLA-A2 mouse transgenic islets and allogeneic human PBMC provide an effective in vivo model of human islet allograft rejection.
Banuelos, S J.; Shultz, L D.; Greiner, D L.; Burzenski, L M.; Gott, B; Lyons, B L.; Rossini, A A.; and Appel, M C., " 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." (2004). Faculty Research 2000 - 2009. 795.