Regulation of autoimmune disease physiological and therapeutic.

An important question is how the immune system can control the behavior of autoimmune effector lymphocytes. My colleagues and I have investigated this question in four models. Three models of organ specific autoimmune diseases were studied using the specific autoimmune lines or clones of T lymphocytes functionally involved in the disease process. The fourth model was an anti-idiotypic network triggered spontaneously by autoantibodies. This article reviews the evidence indicating that healthy individuals can carry potentially virulent autoimmune T lymphocytes without symptoms. This carrier state of autoimmunity implies the existence of natural mechanisms of counter-autoimmunity. One natural element appears to be clones of suppressor-inducer T lymphocytes that arise in the course of the autoimmune response. We have discovered that autoimmune effector T lymphocytes can serve as inducers of their own suppression either artificially, by manipulating the T cell membrane, or naturally, by exposing the individual to very low concentrations of some effector T cell clones. Regarding the regulation of autoreactive B lymphocytes, we have observed that spontaneous generation of anti-idiotypic antibodies may have a particular bias for autoantibody idiotypes. Counter-autoimmunity appears to involve recognition of the self-reactive lymphocyte receptors resulting in the activation of suppressor cells. These suppressor cells can prevent disease or cause remission of established disease.