Thyroid-derived epithelial cells acquire alloantigen-presenting capabilities following X-irradiation and class II...

This work was undertaken to further define the antigen-presenting capabilities of thyroid epithelial cells, as this is of paramount importance with regard to their potential to trigger autoimmune thyroiditis. For this purpose we developed the murine cloned thyroid-derived epithelial cell line M.5 which, as previously reported, could be induced to express class II antigens with interferon (IFN)-gamma, but failed to stimulate a primary mixed leukocyte reaction. We now show that M.5 cells acquired alloantigen-presenting function, under conditions in which their replication was arrested by X-irradiation, during a 4-day period of exposure to UV-inactivated reovirus, or to IFN-gamma, for induction of class II antigens. The allostimulatory function by M.5 cells could not be explained on the basis of enhanced class II antigen expression, as equivalent numbers of M.5 cells, irradiated after the 4-day exposure to reovirus, or to IFN-gamma, expressed higher amounts of class II antigens, but did not stimulate a primary mixed leukocyte reaction. Early X-irradiation appeared to induce in the class II-expressing M.5 cells a co-stimulatory signal needed for T cell proliferation, similar to that otherwise provided by phorbol esters in this system. Preservation of alloantigen-presenting function by M.5 cells following fixation indicated that this co-stimulatory activity did not reside in a soluble molecule. We surmise that M.5 epithelial cells must provide a least two signals in order to be able to stimulate lymphocyte populations. Consequently, the mode and conditions of epithelial cell activation may determine whether these cells acquire the capacity to serve as antigen-presenting cells, and ultimately whether or not they are able to induce autoimmune disease.