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. Naïve 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 α4-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.