C. C. Congdon

Thymus specificity in lethally irradiated mice treated with rat bone marrow.

Summary Immunologic and cytologic tests indicate that the thymuses of lethally irradiated mice protected with rat bone marrow are repopulated by rat-type cells. The agglutination tests showed this repopulation of the thymus by donor cells to be 100% complete 30 days after treatment, and the cytologic analysis of dividing cells showed 100% rat-type cells 21 days after treatment. Although the histologic architecture of these thymuses was often normal, recovery of the thymuses in terms of weight was incomplete.

Effect of antigen dose on lymphatic tissue germinal center changes.

Summary Investigations were performed on the effect of various doses of sheep erythrocyte antigen on spleen germinal center changes. These changes were correlated with the production of specific serum antibody during the first 30 days after primary antigen stimulation. The results indicate a dose-response relationship between antigen dose and germinal center changes. A correlation was observed between the germinal center changes and specific serum antibody production.

A fatal reaction caused by implantation of adult parental spleen tissue in irradiated F1 mice.

Summary 1) Implantation into irradiated F1 hybrids of viable spleen cells from non-irradiated adult mice of the parental strains caused death within 2-4 weeks. 2) The fatal reaction occurred even after sublethal doses of radiation or when the recipients were also injected with marrow cells from isologous hybrids or from mice of the same strain as that from which the parent-strain spleen tissue was obtained. The deaths are ascribed to the formation by the implanted cells of antibodies against the recipient.

ABNORMAL IMMUNE MECHANISM IN ALLOGENEIC RADIATION CHIMERAS.

Mice were subjected to x-rays (950 roentgens) and injected with isogeneic (isologous) or allogeneic (homnologous) bone marrow. Six to 8 months later these chimeras were injected with Salmonella typhi flagellar antigen, and the formation of antibodies resistant and sensitive to destruction by treatment in vitro with 2-mercaptoethanol was determined. The allogeneic chimeras showed almost normal amounts of serumn antibody after a third injection of antigen but a relative defect in their ability to synthesize antibody resistant to 2-mercaptoethanol. Apparently control of antibody formation becomes abnormal in the presence of the immunologic tolerance existing between the host and the foreign hematopoietic graft.

Spleen Weight as a Measure of Marrow Cell Growth in Irradiated Mice.

Summary C57BL, C3H, C57BL/6, and DBA/2 parental marrow cells were injected at varying doses into lethally irradiated BC3F1 and B6D2F1 mice. Spleen weight in recipients was compared to spleen colony formation and Fe59 uptake. Results showed that increased spleen weight was proportional to formation of increased numbers of splenic nodules and percentage of Fe59 uptake. Data suggest that spleen weight, spleen colony formation, and Fe59 uptake are equally suitable assays, within appropriate limits, for studies on proliferation of marrow cell transplants in irradiated mice. Spleen weight is a useful index of growth for doses of transplanted marrow cells which promote recovery of hematopoietic injury in lethally irradiated mice.

Effect of foreign fetal and newborn blood-forming tissues on survival of lethally irradiated mice.

Summary Lethally irradiated mice that received blood-forming cells from homologous fetal liver showed better long-term survival and lymphatic tissue recovery, than those treated with blood-forming cells from adult homologous bone marrow. In both cases there was transplantation and persistence of erythropoietic cells.

DONOR-TYPE LYMPHATIC TISSUE CELLS IN LETHALLY IRRADIATED MICE TREATED WITH HOMOLOGOUS FETAL LIVER

Normal lymph node structure was found in lethally irradiated LAF/sub 1/ mice treated with homologous 101C3F/sub 1/ fetal liver cells. Specific cytotoxic antisera prepared against host-type cells failed to react with bone marrow and lymph node cells. The conclusion is drawn that these cells are of donor origin. (auth)

Effects of immunized parental strain bone marrow on lethally irradiated F1 hybrid mice.

Summary Pre-sensitization of parental strain donor mice against F1 hybrid recipients accentuated the foreign bone marrow reaction caused by injection of parental marrow cells into lethally irradiated F1 recipients. This effect occurred with use of parental strains (101 and C3H) that were histocompatible at the H-2 locus, as well as with those (C57BL and 101) that were histoincompatible at this locus. These results are interpreted to indicate the importance of relative antibody-forming potency of implanted cells, as well as the extent of histocompatibility differences in pathogenesis of the homograft reaction.

Effect of thymus transplantation on radiation chimeras.

Recent evidence points to the thymus of the neonatal mouse as the embryologic source of stem cells for the immune mechanism of the adult animal, even though the fetal thymus itself lacks immunological competence (Auerbach, 1961; Miller, 1961, 1962; Martinez, 1962). There is no reason to think that the large thymus of the young adult animal, or even the atrophic thymus of the old animal, does not continue to be a significant factor in the function of the immune mechanism (Congdon and Duda, 1961; Swartzendruber et al., 1961; Congdon and Doherty, 1963; Miller, 1962). Evidence that the adult thymus might disburse its cells to function immunologically in other sites, such as spleen and liver, has been reported by Fichtelius (1953). Four different kinds of protection and recovery experiments are pertinent to the study of thymic function in the young adult mouse. The first of these concerns chemically protected animals. In lethally irradiated mice protected with AET, thymus regeneration precedes by several days regeneration of the other lymphatic tissues, thus allowing one to speculate that the thymus in the adult animal might be the source of the regenerated tissue. These findings were based on histologic evidence of recovery rather than tissue weight changes (Congdon and Doherty, 1963). In another type of experiment, injection of isologous thymus cells into normal mice did not produce detectable histologic changes in the host thymus or the lymphatic tissues. However, in irradiated mice marked accumulation of the thymocyte-like cells appeared in the spleen red pulp after intravenous injection of many millions of thymus cells. When an antigenic stimulus was provided, many antibody-forming cells developed in the red pulp, perhaps by transformation from the thymus cells (Congdon and Duda, 1961). In a third experiment, direct identification of thymus cells in rat bone marrow chimeras was made. It was noted that the initial regeneration of thymocytes was of mouse host type, according to the identification system used (Gengozian et al., 1957). Later, only thymocytes of rat type were identified. It is conceivable these could then give rise to a rat im-

Influence of radiation dose on induction of the foreign spleen reaction in f1 hybrid mice.

Parental spleen cells were injected into several strains of F/sub 1/ hybrid mice given 0 to 900 r of whole-body x radiation, and the survival, clinical appearance, and histologic changes in the recipients were studied. With two exceptions there was a threshold level of radiation below which there was no mortality. This radiation level varied with the donorrecipient strain combination, being lower in those with more marked histoincompatibility. The mortality was associated with a granulomatous reaction in lymphoid organs, atrophy of hemopoietic tissues, and outward signs of illness. Mortality occurred earlier following higher irradiation doses. Strain variations in ultimate mortality were noted. (auth)