Murine Experimental Autoimmune Orchitis (EAO) Induced by Syngeneic Testicular Germ Cells (TC) Alone: Orchitogenic and Lymphostimulatory Activities of TC from Mice at Various Ages

Abstract

As part of our continuous investigations on the immune pathogenesis of a new experimental autoimmune orchitis (EAO) model without the use of adjavant in C3H/He mice, the developmental patterns of autoantigenicity of viable syngeneic testicular germ cells (TC) during the postnatal period were investigated by examining the orchitogenic and immunogenic activities of TC, the lymphostimulatory activities of TC (the cytokine release from sensitized spleen cells (SPC) in response to TC), and the immunohistochemical localization of autoantigens in the testes of normal mice at various weeks of age. TC from 6-week-old mice had the capability of inducing EAO (orchitogenicity) for the first time. Delayed-type hypersensitivity-inducing capacity and antiTC antibody-eliciting capacity were initially observed in mice immunized with TC from 4-week-old mice. A significant stimulation of interleukin 5 (IL-5) and interleukin 6 (IL-6) production by sensitized SPC was detectable when the TC from 3-week or older mice were employed as a stimulant. Interleukin 2 (IL-2) and interferon-γ (IFN-γ) production was detected with TC from 4-week or older mice. Immunohistochemical staining reaction with anti-TC antisera was primarily localized at the acrosomal portion of spermatids and spermatozoa in the seminiferous tubules and was detected in early and late spermatids of mice as early as 3 weeks. Thus, from these chronological data it is suggested that the appearance of the lymphostimulatory activities of TC consistently precedes that of the orchitogenic activity and that the production of IL-5 and IL-6 (Th 2 cytokine) by sensitized SPC upon in vitro TC stimulation is detectable earlier than the production of IL-2 and IFN-γ (Th 1 cytokine) in the postnatal period.