A key role for ICAM-I in generating effector cells mediating inflammatory responses

We investigated how the accessory molecule interactions encountered during T cell priming influence T cell-mediated destruction of insulin-producing b eta cells and lead to type I diabetes. T cell receptor (TCR)-transgenic CD4 (+) T cells were primed under controlled conditions in vitro before being a doptively transferred into transgenic recipients expressing membrane ovalbu min under the control of the rat insulin promoter (RIP-mOVA), During primin g, antigen-presenting cell expression of B7-1 without intracellular adhesio n molecule 1 (ICAM-1) led to the generation of effector cells that migrated to the pancreata of RIP-mOVA recipients but did not cause diabetes. In con trast, when T cells were primed with APCs expressing both B7-1 and ICAM-1, pronounced destruction of beta cells and a rapid onset of diabetes were obs erved. Pathogenicity was associated with T cell production of the macrophag e-attracting chemokines CCL3 and CCL4. Thus, interactions of lymphocyte fun ction-associated antigen 1 with ICAM-1 during priming induce both qualitati ve and quantitative alterations in T effector function and induce potential ly autodestructive responses.