H. Sobis

Prevention of murine experimental allergic encephalomyelitis: cooperative effects of cyclosporine and 1 α, 25-(OH)2D3

The hormone 1 alpha, 25-dihydroxyvitamin D3 (1,25(OH)2D3) has immune modulatory activities in vitro and in vivo, and can prevent or delay the onset of experimental or spontaneous autoimmune diseases. At therapeutical doses, however, hypercalcemic side effects are found. The present experiments examined the effects of combined treatment with subtherapeutic doses of cyclosporine A (CsA) and 1,25(OH)2D3 on the evolution of experimental autoimmune encephalomyelitis (EAE) in SJL mice. 1,25(OH)2D3 at 5 micrograms/kg body weight (given by i.p. injection every 2 days) prevented the appearance of paralysis in 70% of the treated mice. The treatment with 1,25(OH)2D3 at 2 micrograms/kg/2 days alone had less substantial protective effects (22% disease-free animals versus 5% in the control group). However, when this subtherapeutic dose was associated to treatment with a daily dose of CsA (2 or 5 mg/kg/day), which by itself was subtherapeutic (24 and 50% disease-free animals, respectively), the association of both drugs led to near-total protection (86% disease-free animals when combined with the highest dose of CsA). When an alternate day administration schedule (CsA at 10 mg/kg and 1,25(OH)2D3 at 2 micrograms/kg, each given on alternate days from day -3 to +19 after disease induction) was used, all treated mice were completely protected clinically and histologically. The two drugs also showed additive effects on serum osteocalcin and urinary calcium and desoxypyridinoline excretion, but not on serum calcium concentration. Our experiments demonstrate that 1,25(OH)2D3 might be a potential dose-reducing agent for CsA in immunosuppressive therapy.

Effect of staphylococcal enterotoxin B injection on the development of experimental autoimmune encephalomyelitis: influence of cytokine and inducible nitric oxide synthase production

Possible mechanisms involved in the protective effect of staphylococcal enterotoxin B (SEB) injection on the subsequent development of experimental autoimmune encephalomyelitis (EAE) were investigated. Only partial clonal deletion and anergy of Vbeta8 + T-lymphocytes were documented after myelin basic protein immunization in SEB injected mice. Brain permeability was not influenced. Within the brain or during in vitro rechallenge assays SEB protected mice produced significantly more IL-10, IL-4, TNF-alpha and iNOS. It is suggested that the immune deviating effect of SEB may be involved in its EAE protective effect.

Experimental rat model for human yolk sac tumor

The morphological and biological characteristics of experimentally induced rat yolk sac carcinomas (ysca) are compared to those of human yolk sac tumors. It is shown that the rat ysca shares many morphological and biological properties with its human counterpart although the cellular origin is probably different. Whereas the human yolk sac tumors are believed to be of germ cell origin, the rat visceral yolk sac-derived tumors are not. The hypothesis is formulated that the rat ysca are derived from multipotential cells different from germ cells, and which originate in the extra-embryonic membrane after displacement.

The Influence of Local Immune Suppression on Polyoma Virus-Induced Vascular Tumors

The induction of tumors by polyoma virus is very much dependent upon the cell-mediated reaction of the host. In rats and mice this oncogenic virus only induces tumors when inoculated at birth or into immunosuppres-sed animals (1,2). Normal adult rodents are totally resistant to polyoma oncogenesis. Yet, the injection of polyoma (Py) virus into the placenta of fetectomized rats induces vascular tumors of yolk sac origin (3). The development of vascular tumors in these adult rats may result from : (a) the non-immunogenicity of these vascular tumors; (b) the special immunological mother-fetus relationship that exists during pregnancy; and (c) a particular sensitivity of the visceral yolk sac to neoplastic transformation that may eventually be linked to the growth and differentiation potential of the cells in this extra-embryonic membrane.

Neoplastic transformation of the rat visceral yolk sac by polyoma virus

The transforming activity of polyoma virus was verified in vitro in organ cultures of 12-day old rat visceral yolk sacs and embryos. Organ cultures of 18-day old fetal organs were also included. The transforming capacity of the virus was found to be restricted to the endothelial cells of the rat visceral yolk sac. The neoplastic endothelial cells are readily transplantable and possess the polyoma tumor-specific transplantation antigens (TSTA).