A novel model of allograft rejection: immune reconstitution of Rag-1 recipients with 2C transgenic T-cell receptor lymphocytes.
The complexity of allorejection (cell activation, homing, and effector function) makes detailed studies difficult. We have developed a model of allograft rejection using purified monoclonal alloreactive effector cells. Immunodeficient C57Bl/6-Rag-1 (H-2(b)) recipients of Balb/c (H-2(d)) islet or skin grafts were reconstituted via adoptive transfer of splenocytes from 2C transgenic mice containing CD8+ cytotoxic effector cells directed against L(d). Recipients were assessed for engraftment, activation and homing of effector cells, and ability to reject grafts. Both unpurified 2C splenocytes and purified 2C/CD8+ cells durably reconstitute immunodeficient mice. Naive 2C effector cells reject skin grafts, but not islet allografts. However, when effector cells are primed prior to reconstitution, islet allografts are rejected. Using this model, blockade of adhesion molecules LFA-1 and alpha4-integrin delayed infiltration of islet allografts and prolonged allograft survival. This model of allorejection may be useful to study the activation and homing of allospecific cells in vivo.
Ninova
Dora
D
The Transplant Immunology Laboratory, Division of Transplant Surgery, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
Dean
Patrick G
PG
Deeds
Michael
M
Stegall
Mark D
MD
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D017074:Common Variable Immunodeficiency / Q000276:immunology; D005434:Flow Cytometry; D018398:Homeodomain Proteins / Q000235:genetics*; D016381:Islets of Langerhans Transplantation / Q000276:immunology* / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023421:Models, Animal; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D016038:Skin Transplantation / Q000276:immunology*
D018398:Homeodomain Proteins; D011948:Receptors, Antigen, T-Cell; C064658:RAG-1 protein