ABSTRACT
BACKGROUND: The recently identified autonomous mouse parvovirus designated mouse parvovirus-1 (MPV-1) persists in adult BALB/c mice for at least 9 weeks, infects lymphoid tissues, interferes with the ability of cloned T cells to proliferate, and exhibits immunomodulatory properties. As a consequence of these findings, the present studies were undertaken to characterize further the inmunomodulatory effects of MPV-1 on T cell-mediated immune responses in vivo and in vitro. METHODS: To evaluate the effect of MPV-1 infection on CD8+ T cell-mediated responses, BALB/c-H2dm2 mice were infected after transplantation of allogeneic BALB/c skin. RESULTS: MPV-1 potentiated the rejection of allogeneic skin grafts. This potentiation was not a result of virus infecting the cellular or vascular component of the graft as determined by in situ hybridization, but was mediated by T cells. However, the proliferative capacity of alloantigen-reactive lymphocytes from graft-sensitized infected mice was diminished. MPV-1 also induced the rejection of syngeneic skin grafts, and T cells from these infected graft-sensitized mice lysed syngeneic P815 target cells. CONCLUSIONS: These results suggest that MPV-1 infection of skin-grafted mice may disrupt normal mechanisms of peripheral tolerance and provide a unique model to study virus-induced autoimmunity.
Subject(s)
Graft Rejection/immunology , Parvoviridae Infections/immunology , Skin Transplantation/immunology , Animals , Autoimmunity/immunology , Cell Division/immunology , DNA, Viral/analysis , Mice , Mice, Inbred BALB C/genetics , Mice, Mutant Strains/genetics , T-Lymphocytes/cytology , T-Lymphocytes/immunology , Transplantation, Homologous/immunology , Transplantation, Isogeneic/immunology , Virion/geneticsABSTRACT
Most inbred strains of mice, including DBA/2 (D2), are highly susceptible to the lethal effects of ectromelia virus, but C57BL/6 (B6) mice are innately resistant. Resistance is controlled by multiple, unlinked, autosomal dominant genes. Of 101 male (B6 x D2)F1 x D2 backcrossed (N2) mice, 18 died after ectromelia virus challenge and all were homozygous for the D2 allele at the proline-rich protein (Prp) locus on distal chromosome 6 (P < 0.001). This association was suggested by the patterns of susceptibility to lethal mousepox in recombinant inbred strains derived from B6 and D2 mice (D. G. Brownstein, P. N. Bhatt, L. Gras, and R. O. Jacoby, J. Virol. 65:1946-1951, 1991). The association between the Prp locus and susceptibility to lethal mousepox also held for N2 male mice that were castrated as neonates, which increased the percentage that were susceptible to 40. Spleen virus titers were significantly augmented in B6 (NK1.1+) mice depleted of asialo GM1+ or NK1.1+ cells, whereas spleen virus titers were unaffected in D2 (NK1.1-) mice depleted of asialo GM1+ cells. These results suggest that a gene or genes within the natural killer gene complex, adjacent to the Prp locus, determine strain variations in resistance to lethal ectromelia virus infection.
Subject(s)
Chromosome Mapping , Ectromelia, Infectious/immunology , Immunity, Innate , Killer Cells, Natural/immunology , Poxviridae/physiology , Virus Replication , Animals , Crosses, Genetic , Disease Susceptibility/immunology , Female , Genes, Dominant , Genetic Linkage , Genetic Predisposition to Disease , Male , Mice , Mice, Inbred C57BL , Mice, Inbred DBA , Mice, Inbred Strains , Poxviridae/immunology , Species SpecificityABSTRACT
Hematuria in rabbits has been associated with uterine adenocarcinoma, uterine polyps, renal infarction, urolithiasis, cystitis, bladder polyps, and pyelonephritis. Three adult female New Zealand White rabbits (Oryctolagus cuniculus) developed apparent hematuria, as suggested by blood in their excreta pans. They had been immunized with antigen-adjuvant emulsions, but had uneventful clinical histories. Physical examination disclosed no abnormalities, and laboratory tests, including hematology, serum chemistries, urinalyses, urine cultures, ultrasonography, and intravenous pyelography disclosed mild anemia, hematuria, and proteinuria in two of the rabbits. Antibiotic therapy failed to alleviate clinical signs. Two rabbits were euthanized because of persistent urogenital bleeding and the third rabbit underwent exploratory laparotomy and ovariohysterectomy. Multiple endometrial venous aneurysms were present in the uteri of all rabbits and urogenital bleeding was attributed to episodic bleeding from these lesions. Varices and aneurysms of uterine subserosal and myometrial venous plexuses, but not of endometrial vessels in women have been reported. To our knowledge, endometrial venous aneurysms have not been reported in animals previously. Our findings indicate that the differential diagnoses for sporadic apparent hematuria in female rabbits should include endometrial aneurysms.
Subject(s)
Aneurysm/veterinary , Endometrium/blood supply , Hematuria/veterinary , Rabbits , Aneurysm/complications , Aneurysm/pathology , Animals , Endometrium/pathology , Female , Hematuria/etiology , VeinsABSTRACT
The uptake mechanism of two potential cardiac imaging agents [99mTc]hexakis(t-butylisonitrile) technetium (I) (TBI) and [99mTc]hexakis(isopropylisonitrile) technetium (I) (IPI) has been studied using neonatal rat myocytes and human erythrocytes. Uptake of these complexes was rapid, of greater magnitude than seen previously for 42K, and was unaffected by either 0.15 mM ouabain or 10 mM KCI. Both [99mTc]isonitrile complexes had a high affinity for the membranes of the myocytes and erythrocytes. The data suggest that the uptake is not dependent on the membrane Na+/K+ ATPase but may be related to the lipophilicity of these agents as evidenced by the rapidity, tenacity, and quantity of the binding observed.
Subject(s)
Erythrocytes/metabolism , Heart/diagnostic imaging , Myocardium/metabolism , Nitriles/metabolism , Organometallic Compounds/metabolism , Organotechnetium Compounds , Technetium/metabolism , Animals , Animals, Newborn , Cell Membrane/metabolism , Humans , Nitriles/blood , Organometallic Compounds/blood , Ouabain/pharmacology , Potassium/pharmacology , Radionuclide Imaging , Rats , Technetium/bloodSubject(s)
Muscles/metabolism , Organotechnetium Compounds , Phosphines/metabolism , Potassium/metabolism , Technetium/metabolism , Thallium/metabolism , Animals , Animals, Newborn , Biological Transport , Cells, Cultured , Kinetics , Muscles/cytology , Potassium Radioisotopes , Radioisotopes , RatsABSTRACT
The ability of isolated human erythrocytes to exchange Na+ for K+ via (Na+ + K+)-ATPase was used to study the characteristics and interactions of the transport of both alkali metal and synthetic monovalent cations. Both efflux and influx studies were carried out and the results showed that: (1) Efflux of 22Na+ from human erythrocytes was stimulated by the addition of either of K+, or Tl+ at 10 mM and inhibited by the addition of ouabain. Unlabeled K+ and the addition of [99Tc(dmpe)2 X Cl2]+ (dmpe, 1,2-bis(dimethylphosphino)ethane) at 5 mM had no effect on 22Na+ efflux. (2) Influx of 42K+ was inhibited by the addition of ouabain, unlabeled K+, or Tl+. 201Tl+ influx was more rapid and of a greater magnitude than 42K+ influx. [99Tc(dmpe)2 X Cl2]+ had no effect on 42K+ uptake. (3) Influx of 201Tl+ was inhibited by ouabain and by the addition of unlabeled Tl+. Addition of [99Tc(dmpe)2 X Cl2]+ at 5 mM resulted in an inhibition of 201Tl+ influx. (4) [99Tc(dmpe)2 X Cl2]+ influx resembled that of 42K+ with respect to rate and magnitude. Influx of [99mTc(dmpe)2 X Cl2]+ was shown to be unaffected by ouabain, unlabeled K+ or Tl+. Addition of 5 mM [99Tc(dmpe)2 X Cl2]+ initially had no effect on [99mTc(dmpe)2 X Cl2]+ influx, however, a time-dependent stimulation of the influx of the [99mTc(dmpe)2 X Cl2]+ was observed. We conclude that the influx of the various alkali, metal and synthetic monovalent cations into erythrocytes is mediated by different mechanisms. Most clearly, the influx of [99mTc(dmpe)2 X Cl2]+ is not by a mechanism similar to that of utilized by K+ or Tl+.