Immune system activation in C3H/HeJbir mice exhibiting spontaneous perianal ulceration

Abstract

: We report our initial characterization of the immune system in C3H/HeJBir mice that spontaneously develop perianal ulceration. Analysis of lymphokine production by mucosal and systemic lymphoid cells obtained from these mice revealed higher levels of interleukin (IL)4 in supernatants of in vitro stimulated Peyer's patch and mesenteric lymph node cells from C3H/HeJBir mice with severe perianal lesions than from C3H/HeJBir mice with mild perianal lesions or from normal C3H/HeJ mice. Supernatants that contain the highest amounts of IL-4 contain the lowest amounts of interferon (IFN)-γ. Peyer's patches and mesenteric lymph nodes of C3H/HeJBir mice with severe perianal lesions contain approximately four-fold fewer cells; however, inguinal lymph nodes contain up to 25-fold more cells compared with C3H/HeJ mice. These inguinal lymph node cells secrete IL-6, and T cells that produce IL-2 or IFN-γ can be demonstrated. Serum IgE, IgGl, and IgG2a are all increased in C3H/HeJBir mice with severe perianal ulceration. These results show that C3H/HeJBir mice with grossly evident inflammation have activated lymphocytes in both mucosal and systemic lymphoid organs. Understanding mechanisms of lymphocyte activation and regulation in these mice may provide insights into the pathogenesis of perianal ulceration that is often associated with Crohn's disease.