T lymphocyte control of autoreactivity: analysis with human T cell clones and limiting dilution culture

To investigate cellular mechanisms controlling activated autoreactive T lymphocytes, a limiting dilution system was established employing cloned autoreactive major histocompatibility complex class II specific lymphocytes (a2/7) as stimulator cells for autologous peripheral blood mononuclear cells. At low responder/stimulator ratios, cytotoxic effector cells were generated capable of lysing clone a2/7. Importantly, within the population of cells mediating autocytotoxic effector function, differential specificities were found to exist. The generation of such autocytotoxic T lymphocytes appears to be inhibited by an additional population of cells circulating at lower frequency suggesting that autoreactivity is controlled at distinct levels by discrete functional cellular subsets.