Histocompatibility requirements for cellular cooperation in the chicken.
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Biomedical subjects
Publications and source records attributed to A Toivanen.
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The ontogeny of alkaline phosphatase in the bursa of Fabricius was studied by histochemical and biochemical methods. According to the quantitative determinations, the activity of alkaline phosphatase increased from the 11th to 17th day of incubation--that is, during the time of the lymphoid follicle formation in the developing bursa. The activity was localized in the mesenchymal tissue surrounding the lymphoid follicles. Testosterone given in ovo prevented the appearance of alkaline phosphatase in the bursal mesenchyme but had no effect on the activity of the embryonic liver. In contrast, in ovo treatment with cyclophosphamide had no effect on the alkaline phosphatase in the bursa. By using transplantation of embryonic bursal stem cells, it was further shown that, in contrast to cyclophosphamide, testosterone destroys the capacity of the bursa to serve as a differentiation site for the B-cell lineage. The results indicate that testosterone affects the stromal cells of the bursa, whereas cyclophosphamide destroys only the lymphoid population undergoing differentiation and leaves the bursal stroma intact.
Cyclophosphamide-treated newly hatched chicks were transplanted with histocompatible, semiallogeneic and allogeneic combinations of B (bursa) and T (thymus) cells from newly hatched donors. At the age of 5 weeks the birds were studied for an anti-SRBC response and for the generation of germinal centers in the spleen. The results of these experiments are summarized as follows. i) Allogeneic bursal stem cells have the capacity to restore the bursal structures of CY-treated recipients, but not the germinal center or anti-SRBC formation. ii) When allogeneic B cells are combined with T cells histocompatible or semiallogeneic with them, a restoration of the germinal center formation is achieved, but not to the same level as observed in normal birds or in CY-treated birds transplanted with histocompatible or semiallogeneic B cells. iii) Allogeneic B cells, even when complemented with T cells histocompatible with them, fail to restore the antibody production against SRBC; this is achieved only after transplantation of B cells histocompatible or semiallogeneic with the recipient. These findings indicate that germinal center formation is dependent on cooperation of histocompatible or semiallogeneic B and T cells, and furthermore, that an additional factor provided by the host is involved. Studies with transplantation of histocompatible and histoincompatible 'empty' splenic stromata revealed that the additional factor is not related to the splenic stroma.
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After transplantation of bursal stem cells into cyclophoshamide-treated newly hatched chicks, the first lymphoid cells in the spleen of the recipients were observed on the first day after the cell transfer and the first plasma cells on day 3. The repopulation of the Schweigger-Seidel sheaths started from their periphery on day 6. The first germinal centers were detected 20 days after the cell transfer. In cyclophosphamide-treated birds without cell transplantation, only the periphery of the Schweigger-Seidel sheaths became repopulated, and no plasma cells or germinal centers were observed. The results indicate that already at the age of 3 days the bursa contains some cells of postbursal maturity, able to home to the spleen.
The occurrence of drug-resistant coliform bacteria was studied in the faecal flora of 30 persons receiving for 3 weeks either trimethoprim alone, a combination of sulphamethoxazole and trimethoprim, or a combination of sulphamethoxydiazine and sulphamethoxazole. Bacterial sensitivity was tested against trimethoprim, sulphamethoxazole-trimethoprim, sulphamethoxazole, and sulphaisodimidine. After treatment with trimethoprim alone, no increase in the occurrence of strains resistant to either trimethoprim or sulphonamides was observed. After treatment with sulphamethoxazole-trimethoprim, the faecal flora contained an increased percentage of sulphonamide-resistant coliforms but significantly less than found after treatment with sulphamethoxydiazine-sulphamethoxazole. In the persons receiving the sulphonamides only, a rapid increase in sulphonamide-resistant coliforms was observed. During the whole study, only one trimethoprim-resistant coliform strain was detected.
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Antibodies against milk protein were sought by a radioimmunoassay in 47 patients with myocardial infarction and in 50 control patients. There was no difference between the two groups in the frequency or in the quantity of IgM and IgG antibodies against milk proteins. These results do not support the suggestion that anti-milk antibodies are involved in the pathogenesis of coronary heart-disease.
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For transplantation of semiallogeneic bursal stem cells into cyclophosphamide-treated 3-day old chicks, two lines of chickens homozygous at the major histocompatibility locus and their F(1) hybrids were used in reciprocal combinations. The semiallogeneic transplantations resulted in a complete restoration of antibody formation to sheep red blood cells (SRBC) and Brucella, of microscopic morphology of bursa fabricii, and of germinal center formation in the spleen. In contrast, allogeneic bursal stem cells were not effective in restoring secondary response to SRBC and germinal center formation, while they were able to reconstitute anti-Brucella responses and bursal morphology. These findings indicate an effective cooperation of donor and host cells leading to a complete restoration of the bursa-dependent lymphoid system, when the donor and recipient share at least one haplotype determining the major histocompatibility antigen complex.
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Transplantation of allogeneic cells from bursa of Fabricius into cyclophosphamide-treated, immunodeficient chicks resulted in immunological tolerance to donor line skin grafts; graft-versus-host disease did not occur. Allogeneic bursal stem cells taken from 3-day-old donors induced restoration of bursal morphology, of antibody formation to Brucella abortus and of occurrence of pyroninophilic cells and immunoglobulin-bearing cells in the peripheral lymphoid tissues. Secondary response to sheep red blood cells and production of germinal centers were not restored. Transplantation of histocompatible bursal stem cells resulted in a complete reconstitution of the bursa-dependent lymphoid system, both in function and in morphology. Allogeneic postbursal stem cells taken from the bursa of 10-week-old donors had a reconstitutive effect only on the production of antibodies to Brucella. Transplanted stem cells maintained their functional potential in the allogeneic environment, since, when transferred back to histocompatible hosts, they displayed normal function. These findings indicate that a complete functional and morphological restoration of the bursa-dependent immune system cannot be achieved without identity of the donor and recipient at loci near to or identical with those determining the major histocompatibility antigens, even though graft-versus-host disease is avoided. This identity permits a full cooperation of the donor and host cells.