Jane I. Morton

Vitamin C and the immune response.

The inclusion of vitamin C in the drinking water of BALB/c mice was without effect on the humoral antibody response to sheep red blood cells and bacterial lipopolysaccharide. However, there was a significantly increased cell-mediated immune response as determined by increased T-lymphocyte responses to concanavalin A. This might suggest a mechanism, along with interferon enhancement, for the possible protection by vitamin C against some viral infections.

Serum Agglutinin Levels to Sheep Red Blood Cells in Mice Infected With Rauscher Virus.

Summary Primary agglutinin liters were depressed in mice immunized with sheep red blood cells 8 days or more following inoculation of l0-1 or 10-2 dilutions of Rauscher leukemogenic virus. The extent of depression was proportional to virus dose and could frequently be detected before the appearance of hematological evidence of leukemic development. Immunization 7 days before, at the time of, or 4 days after, viral inoculation did not result in depression of primary titers. In all these instances a lag was noted in antibody response 4 days after the secondary stimulus; however, by 7 or 8 days increases in antibody titers over primary levels were similar in both virus and control groups. Even in mice markedly leukemic at the time of secondary challenge no depression of the secondary response was observed. A possible mechanism concerning the influence of viral leukemogenesis on the immune response is discussed.

Transplantation of autoimmune potential. II. Glomerulonephritis in lethally irradiated DBA/2 recipients of NZB bone marrow cells.

Lethally irradiated (850 rads) DBA/2 mice which had been transplanted 10 months previously with 2 x 106 bone marrow cells from 3-week-old donors of the H-2-histocompatible NZB, BALB/c and DBA/2 strains were examined for manifestations of autoimmune disease. Also studied were lethally irradiated (950 rads) NZB mice grafted with NZB marrow. Strongly positive antinuclear antibody responses were present in all NZB and DBA/2 recipients of NZB marrow, but absent in DBA/2 mice grafted with BALB/c and DBA/2 marrow cells. The antinuclear antibody-positive animals had glomerulonephritis with the deposition of globulin in or along the basement membranes. These observations support the view that the potential for autoantibody formation and subsequent autoimmune disease development is inherent to the NZB hemopoietic stem cell and their progeny.

TUMOR VIRUS EFFECTS ON IMMUNOCYTE PRECURSOR CELLS. HEMOPOIETIC STEM CELL BEHAVIOR AND LEUKEMOGENIC SUSCEPTIBILITY

Studies of Rauscher virus-induced erythroleukemia have demonstrated immunodepressive effects in the host and enhanced leukemogenesis with adjuvant administration. These observations led to the study of leukemic development in the NZB strain as a natural model of the experimentally adjuvant-stimulated animal. The results of such investigation would attribute the increased susceptibility of NZB mice to the possession of an enlarged population of pluripotent hemopoietic stem cells in active cell cycle. Studies with radiation chimeras have further shown that elevated endogenous spleen colony formation, the increased potential for autoimmunity, and for susceptibility to Rauscher viral leukemogenesis are all linked through the NZB hemopoietic system. It is concluded that the presence of an enlarged compartment of cyclically active stem cells may be an etiologic factor in the susceptibility to both virus-induced leukemia and the development of autoimmune disease.

Hematological changes in mice following freund's adjuvant administration.

A single intraperitoneal injection of mice with complete Freunds adjuvant, with and without bovine serum albumin, resulted in transient involution of the thymus and spleen, a wasting syndrome, and an altered peripheral blood picture characterized by lymphopenia and neutrophil granulocytosis. Interestingly, an increased production of antibody was observed during a period of reduced lymphocyte numbers. An analogy has been drawn here to the wasting disease observed in neonatally thymectomized mice.

Reticuloendothelial activity of new zealand black mice.

Summary Carbon clearance rates were observed to be significantly increased in autoimmune NZB mice with enlarged spleens. Similar acceleration could be induced in young NZB mice by intraperitoneal injection of phenylhydrazine 5 days prior to assay. Marked anemia and splenomegaly were also noted to develop following such phenylhydrazine treatment. Splenectomy of 1-year-old NZB mice was observed to result in delayed clearance of carbon particles. There was little effect on the rate of carbon clearance in young NZB mice injected intraperitoneally with a serum pool obtained from old Coombs positive animals. Assessment of spleen and liver radioactivity following intravenous injection of technetium-99m sulfur colloid indicated a somewhat reduced efficiency of colloid uptake by the enlarged spleen on a per milligram weight basis; however, this reduced efficiency was not sufficient, generally, to counteract the increased clearance capacity of the whole organ. The present findings would suggest that the increased rate of carbon clearance observed in overtly autoimmune NZB mice may be a result of the hepatosplenomegaly associated with the disease state. We are grateful to Dr. E. L. Dobson, Donner Laboratory, University of California, Berkeley, for supplying the Pelikan carbon and for his helpful discussions regarding these studies.

Retardation of murine viral leukemogenesis by prolonged antigenic stimulation.

Die Mortalität an Leukämie bei BALB/c-Mäusen wurde durch wöchentliche i.p. Injektionen mit menschlichen Erythrozyten herabgesetzt, wenn sie während 8 Monaten vor der Impfung mitRauscher-Leukämievirus vorbehandelt waren. 7 Monate nach der Virusinfektion zeigten 20% dieser Mäuse keine Zeichen von Leukämie. Kontrollversuche mit der gleichen Serie von Injektionen von Ochsenserumalbumin zeigten keinen Schutz.

Influence of Cytoxan and Poly I·C on Early Antinuclear Antibody Responses in New Zealand Black Mice

Summary Early manifestation of antinuclear antibodies (ANA) in the plasma of NZB mice was significantly depressed by twice weekly injection of 20 mg/kg body weight cytoxan from the age of 9 days. Single injection of 75 mg/kg at 6 or at 13 days of age was ineffective in this regard. Similarly, ongoing ANA responses in 4-month-old NZB mice were undiminished by single injection of 180 or 300 mg/kg of cytoxan. A course of administration of 160 μg of poly I·C followed 24 hr later by 75 mg of cytoxan was repeated three times during a period of 56 days in an attempt to induce tolerance in 2-month-old ANA positive mice. Attenuation of ANA response was demonstrable 2 weeks after initiation of treatment, but was not observed at later times during the study, conceivably a consequence of the anti-DNA activity of the antinuclear antibody assayed. We thank Mrs. Sherrie Fitzgerald for her technical assistance.

The Reticuloendothelial System and Tissue Injury

The present topic “The Reticuloendothelial System and Tissue Injury” seems rather too broad and inclusive, since the system recognizably encompasses heterogeneous cells widely scattered throughout the body, providing a variety of functions protective as well as injurious. Tissue injury may result from direct cell-cell contact between sensitized lymphocytes and target cells, or more frequently, may arise secondary to the induction of an inflammatory reaction. Mediators elaborated as a consequence of the immune response bring about a localized accumulation of neutrophils, monocytes, lymphocytes, and plasma constituents which are intimately associated with the tissue damage. The role of the RES in tissue injury thus includes a variegated spectrum of cellular involvement and immune reactions both antibody- and cell-mediated. These are addressed by a number of chapters in this volume. We shall therefore limit this presentation to a brief review of a few of the etiological factors and mechanisms involved in the mediation of tissue injury by the RES.

Circulating hemagglutinins of new zealand black strain mice immunized with sheep erythrocytes.

Es wird gezeigt, dass der Gehalt an Serumantikörpern nach Immunisation mit Schaferythrozyten in jungen NZB-Mäusen im Vergleich zu BALB/c-Stämmen grösser ist. Diese Unterschiede wurden nach der zweiten und dritten Antigeninjektion geringer. Bei alten Coombs-positiven NZB-Mäusen wird eine Verzögerung der Reaktion nach der ersten, jedoch eine normale Reaktionszeit nach der nun folgenden Injektion gefunden. Die Ergebnisse entsprechen den Resultaten mitJernes Technik bei Reaktionsuntersuchungen antikörperbildender Zellen.