Autoreactive T-cell clones from the nonobese diabetic mouse.

The availability of cloned lines of T cells reactive with islet antigens has provided investigators with new tools to study how T cells contribute to autoimmune disease. T-cell clones isolated from the diabetes-prone nonobese diabetic (NOD) mouse are proving to be particularly valuable for analyzing pathogenesis and hold great promise for determining which T-cell subsets are involved in beta-cell destruction versus immunoregulation of the inflammatory process. Diabetogenic T-cell clones have been mostly of the CD4+, Th1 phenotype, but CD8+ T cell clones are also capable of transferring disease. In some cases, T-cell lines and clones (CD4+ and CD8+) have been found to have protective properties. In general T-cell antigen specificities have not been defined, as islet cells or lysates were used as the selecting antigen. However, there is an increasing number of reports of T cells specific for defined islet proteins, such as insulin and GAD, and some of these lines can induce disease. The variety of T-cell clones that have been produced indicate that there may a variety of conditions that lead to or protect against beta-cell destruction and provide further evidence that autoantigens are generated during development of disease.