The role of T cells in the development of arthritis in Inherited Inflamed Joints mice. (148.12)

Abstract

Abstract The IIJ (Inherited-Inflamed-Joints) mouse strain spontaneously develops an inflammatory, possibly autoimmune, arthritis at an early age. While only a third develop disease, incidence displays a distinct female-bias and mice have elevated Ig, autoantibodies, and an increased percent of double negative (DN; CD4-CD8-CD3+) T cells in their secondary lymphoid organs. The goal of our research was to further examine the T cell compartment. The thymi of AR IIJ mice were significantly decreased in size compared to non-arthritic (NAR) IIJ and SJL controls. Flow cytometry revealed significant disregulation in thymocyte subpopulations and immunohistochemistry indicated disrupted cortical/medullary organization. AR IIJ mice also had increased thymic apoptosis based on Annexin V/PI staining and TUNEL assays were performed to investigate the spatial localization of apoptosis. While it remains unclear whether the DN T cells in AR IIJ mice contributes directly to arthritis development, we used flow cytometry to show that they were present in the blood before clinical symptoms began. Finally, since the IIJ strain was originally derived from a transgene-negative mouse from a breeding colony of 5B6 TCR transgenics, we used flow cytometry and PCR to verify the absence of the transgenes. Overall, our studies confirm that IIJ mice have significant disruption in the T cell compartment and that this disruption occurs before onset of clinical disease suggesting a possible causal role in pathogenesis.