Charles D. Severson

Pulmonary "hypersensitivity" reactions induced by transfusion of non-HL-A leukoagglutinins.

Abstract In two cases of normovolemic pulmonary edema associated with whole-blood transfusion, clinical manifestations included abrupt onset of chills, fever, tachycardia, dyspnea and cough. Cyanosis and hypotension occurred in the more severe case, and bilateral pulmonary infiltrates without confirmatory evidence of circulatory overload were present in both. Antibody reacting with recipient leukocytes was identified in the donor serum in both cases by the capillary agglutination technic but not by a standard lymphocyte microcytotoxicity method. Characterization of the antibody in Case 1 revealed that it detected a specificity that was probably not directly related to the HL-A locus, the neutrophil antigens NA1, NB1, NC1 or the 5a–5b locus. Although over five years had elapsed since the last pregnancy, both the responsible donors were multiparous, raising concern about the use of whole blood from multiparous donors particularly when multiple transfusions must be administered.

Assay of human leukoagglutinins by capillary migration.

SUMMARY A new method for assaying human leukoagglutinins has been developed that is a measure of intercellular dissociation and migration of centrifuged leukocytes in capillary tubes by the force of gravity. Comparative studies indicate that the capillary migration method is 10-100 times more sensitive than microscopic agglutination. It, is highly reproducible and rapidly performed. Utilizing sera from the National Institutes of Health serum bank, the method has been adapted for leukocyte typing and cross-matching. The increased sensitivity appears to account for the higher incidence of reproducibly positive responses determined by capillary migration than by microscopic agglutinations. This was most prominent with antisera primarily developed for use in cytoxicity tests. The method is simple, requires no special equipment, and may be partially automated.

Studies on the mechanisms of estradiol-induced radioprotection.

The protective effect of 0.166 mg estradiol benzoate intramuscularly 10 days prior to total body irradiation has been redemonstrated. One milligram estradiol in propylene glycol was as effective as the benzoate, but estrone and estriol were less so and long-acting estradiol compounds were ineffective. Radioprotection conferred by pretreatment with estradiol was associated with stimulation of hematopoietic colonies in the spleen and had no relationship to immunological competence as measured by hemolytic plaque-forming cells to sheep erythrocytes. Since estradiol appeared to reduce the number of stem cells capable of migrating to the spleen and forming new hematopoietic colonies, the beneficial effects appear to be due to daughter cells that arise during the 10 days before irradiation. Whether their apparent resistance is simply due to increased numbers, or to a qualitative change in sensitivity related to cell cycle remains to be answered.

The effect of estradiol and irradiation on the nucleic acid metabolism of the thymus, spleen, lymph node, and liver of mice.

Estrogenic hormones regularly cause acute thymic involution in the intact animal (1, 2). Their effects on lymphatic tissues other than the thymus are minimal, are quite variable, and appear to relate to the species studied. Within the last two years we have investigated the effect of estradiol on lymphatic tissues and the immune system when administered to normal adult, newborn, and sublethally or lethally irradiated mice protected by syngeneic and allogeneic bone marrow. When 0.5 mg of estradiol was given to adult normal female mice, three times weekly over a 6-week peiiod, involution of the thymus occurred within the first week and was marked at 6 weeks (3). Hepatomegaly first appeared within 2 weeks and partially regressed by 6 weeks. Microscopically, this was associated with Kupffer cell hyperplasia, but no other obvious histologic change. The lymph node and the splenic white pulp were not grossly or histologically altered, but there was a slight reduction in the absolute lymphocyte count noted in the peripheral blood after 6 weeks of therapy. Extramedullary hematopoiesis increased within the first week. Anemia, weight loss, and death did not occur. The homograft and hemagglutination responses were unaffected (J. S. Thompson, unpublished data). By contrast, the administration of estradiol to newborn mice induced a wasting syndrome characterized by ruffled fur, diarrhea, weight loss, both central and peripheral lymphoid hypoplasia, and increased mortality (4). Furthermore, if estradiol was injected for 2 weeks after irradiation of adult mice, impaired recovery of the thymus and other lymphatic tissues was associated with increased mortality

STUDIES ON IMMUNOLOGICAL UNRESPONSIVENESS DURING SECONDARY DISEASE. III. EFFECT OF DONOR STRAIN ON ACQUISITION OF MUTUAL TOLERANCE.

A wasting disease that is associated with lymphopenia usually follows the successful transplantation of foreign hematopoietic tissues into lethally irradiated mice. We have attempted to prevent the appearance of this syndrome by injecting immunologically competent lymphoid cells 21 days after irradiation. When irradiated C3H mice were injected with H-2-incompatible C57BL/6 bone marrow, the addition of lymphoid cells 21 days later was never beneficial because a graft-versus-host reaction remained operative. However, when H-2-compatible AKR bone marrow was used to save the life of irradiated C3H mice, the late injection of large numbers of either host or donor lymphoid cells improved subsequent survival and prevented secondary disease. Our experimental results using erythrocyte analysis, the discriminant spleen assay of Simonsen-Jensen, and studies on adoptive immunity to rat erythrocytes as a measure of graft-host interaction all suggest that mutual tolerance develops in C3H-AKR chimeras. This phenomenon appears to explain why added donor or host lymphoid cells were not rejected but instead improved the survival of immunologically incompetent hosts. Tolerance did not exist 48 hr postirradiation, since AKR spleen cells administered at this time killed the C3H-AKR hosts. However, passive immunization with donor antihost antisera 24 hr prior to spleen cell injection allowed some of the mice to survive without further evidence of wasting. Although other explanations are possible, these observations suggest that the acquired AKR-C3H tolerance found in these experiments 21 days postirradiation may have developed because of protective antibodies elaborated by both donor and host cells.

Autoradiographic study of the effect of estradiol and irradiation on nucleic acid metabolism of the thymus and lymph node of mice.

Autoradiographs of

Antileukocyte antibody in postpartum and renal transplant subjects. A comparison of capillary agglutination and lymphocytotoxicity reactions.

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Quantitative semi-micro leuko- and hemagglutination with mouse cells.

and

Induction of Anemia in Female G57B1/6 Mice with Emulsions of Complete Freund's Adjuvant and Erythrocytes∗

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The Effect of Estrogenic Hormones on Immune Responses in Normal and Irradiated Mice

incorporation in the thymus and lymph node have been prepared at intervals from mice after 150 R or 0.5 mg estradiol. Epithelial reticular cells were the primary site of increased incorporation of