Suppressor T Cell Regulation of Autoimmune Thyroiditis

Mullen, Helen

Abstract

The goal of these studies is to develop a model system in which suppressor T cells (TS) specific for an autoantigen, mouse thyroglobulin (MTg) can be induced and assayed for their ability to suppress experimental autoimmune thyroiditis (EAT) in CBA mice. TS will be induced using MTg coupled to syngeneic spleen cells (MTg-SC). T cells from mice given MTg-SC will be first tested for their ability to suppress EAT induced by active immunization of mice with MTg and lipopolysaccharide (LPS). The ability of TS to suppress several distinct steps in the pathway leading to EAT will be examined using a system in which spleen cells from MTg-sensitized mice can be activated in vitro with MTg to become active EAT effector T cells which induce EAT after transfer to normal syngeneic recipients. Using this system, the effect of TS on EAT can be determined at several steps: the in vivo sensitization of effector T cell precursors, their activation in vitro to active EAT effector cells and the interaction of effector T cells with the recipient to induce EAT. TS found to be active in suppressing a given phase of EAT induction will be characterized with respect to the T cell subset to which they belong and the mechanism by which they interact with other cells to suppress EAT will be determined. Finally, we will also determine whether the mode of presentation of MTg by distinct antigen presenting cells can influence the type of T cells (effector or suppressor) which will be activated. The long-term objective of these studies is to obtain information from these basic studies which will increase our understanding of the regulatory mechanisms involved in autoimmune endocrine diseases as well as other autoimmune diseases. When the precise mechanisms underlying the suppression of autoimmunity are better understood, it should be possible to begin to devise more rational and specific approaches for treating autoimmunity in man.