Germ cell-induced immune suppression in mice. Effect of inoculation of syngeneic spermatozoa on cell-mediated immune responses.

Autologous sperm are immunogenic and can elicit cell-mediated immunity and antibody responses (1-4). Immune responses against spermatozoa do not occur under normal circumstances, due to the fact that germ cells are efficiently sequestered from the immune system by the blood-testis barrier (5). This barrier, which is established before the immune system becomes competent, creates an immunologically privileged site for sperm and the developing spermatozoa. Therefore, immunological tolerance is not generated to autologous male germ cells. Injuries of the blood-testis barrier (e.g., after vasectomy, infection, or biopsy) can result in the production of autoantibodies and T cell reactivity (1-4). Because the immune system is not normally exposed to germ cells, it is possible that sperm and other germ cells exert regulatory infuences on immune potential. In the present study, the influence of inoculation of germ cells on cellular immune reactions was investigated. The results indicate that male C5 7BL/6 mice injected with syngeneic germ cells exhibited: (a) reduced natural killer (NK) 1 cell activity; (b) reduced mixed lymphocyte reactivity (MLR); (c) enhanced auto-proliferation; and (d) decreased potential to generate cytotoxic T lymphocyte (CTL) responses to modified self and allogeneic antigens. The reduction in CTL potential against trinitrophenyl-modified syngeneic spleen cells (TNP-self) was mediated by radiosensitive suppressor T cells. These findings are discussed with respect to possible effects of exposure to male germ cells on the immune system. Materials and Methods Animals. Young adult mice (8-12-wk) were used for all in vitro sensitization studies. The inbred strains C57BI6/J (B6), AKR/J, B10.BR (BR), DBA2/J, and (B6 X DBA/2)F1 (BDFI

Resistance of young gelatinase B-deficient mice to experimental autoimmune encephalomyelitis and necrotizing tail lesions

Regulated expression of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) plays a role in various physiological processes. To determine in vivo how unbalanced expression of these factors can promote or affect the course of pathologies, we knocked out the mouse gelatinase B gene by replacing the catalytic and zinc-binding domains with an antisense-oriented neomycin resistance gene. Adult gelatinase B-deficient mice and wild-type controls could be induced to develop experimental autoimmune encephalomyelitis (EAE) with similar scores for neurologic disease, blood-brain barrier permeability, and central nervous system histopathology. However, whereas diseased control animals showed necrotizing tail lesions with hyperplasia of osteocartilaginous tissue, adult gelatinase B-deficient mice were resistant to this tail pathology. Gelatinase B-deficient mice younger than 4 weeks of age were significantly less susceptible to the development of EAE than were age matched controls and, even as they aged, they remained resistant to tail lesions. These data illustrate that gelatinase B expression plays a role in the development of the immune system and that, in ontogenesis, the propensity to develop autoimmunity is altered by the absence of this MMP.status: publishe