Thyroid‐derived epithelial cells acquire alloantigen‐presenting capabilities following X‐irradiation and class II antigen induction

Abstract

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.

Identification of a thyroxine-containing self-epitope of thyroglobulin which triggers thyroid autoreactive T cells.

“…The ability of IFN--y stimulated TECs to activate the hybridoma CH9 without the addition of Tg indicates that the epitope described here can be functionally expressed by thyroid cells, at least in vitro. This observation appears to conflict with other reports (38)(39)(40) that mouse TEC will only present antigen to T cell lines or hybridomas following the induction of a poorly defined costimulatory activity. This discrepancy may simply reflect differences in the costimulator requirements of the cells used ; some T cell hybridomas appear to lack a requirement for costimulatory signals since they can be stimulated by isolated MHC/peptide complexes (41).…”

UVC Radiation-induced Effect on Human Primary Thyroid Cell Proliferation and HLA-DR Expression

“…4 ). It was already shown that human primary thyroid cells increase surface HLA-DR molecules in response to a variety of cell stressors, like IFN-γ [12,28,29] and ionizing radiations [13] or transiently modify HLA-DR expression in vitro in the presence of iodide excess [21] . This local upregulation of antigen-presenting function on thyrocytes in vivo could be sustained by a local infl ammatory network (formed by cytokines and other cells of the immune system) and it may be an early event in the development of AITD [14,30,31] .…”

Causes of Hypothyroidism

“…It has been shown that human primary thyroid cells increase HLA-DR surface expression in response to a variety of cell stressors, such as IFN-gamma (Montani et al, 1998;Otten et al, 1998;Wu et al, 1999) and ionizing radiations (Czirjak et al, 1990) or transiently modify HLA-DR expression in vitro in the presence of iodide excess (Kostic et al, 2009). Recently, Kostic et al (Kostic et al, 2010) showed that HLA-DR expression was also transiently increased 24 hours after UVC treatment of human primary thyroid cells in vitro, and subsequently returned to normal level 48 h after irradiation.…”