Cell-mediated Autoimmunity: Antigen Reactive Lymphocytes recruit Specific Effector Lymphocytes

Abstract

AN individual's immune system is naturally tolerant of his own body's components. Autoimmune diseases are caused by a loss of this self-tolerance and an attack against self-antigens perpetrated by the immune system. The immune damage in such diseases is often mediated directly by auto-sensitized T lymphocytes rather than by antibodies¹. The cellular basis of T lymphocyte self-tolerance has been studied in our laboratory using in vitro methods of autosensitization, and we found that potentially self-reactive lymphocytes exist in healthy rats and mice^2,3. These lymphocytes bear surface receptors which can specifically recognize self-antigens⁴. Tolerance to these antigens, however, appears to be maintained in the intact rat by the action of factors present in normal serum⁵. The factors function specifically to prevent recognition of self-antigens and, therefore, block immune activation of the potentially self-reactive lymphocytes; loss or inactivation in cell culture allows self-recognition and autosensitization. The autosensitized lymphocytes can then produce immune effects ^{in vivo}. Injection of such lymphocytes into the foot pads of syngeneic rats leads to enlargement of the regional popliteal lymph nodes and to the development within these nodes of effector lymphocytes which specifically damage syngeneic but not foreign target cells in culture⁶.