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  • 1
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We studied the early events in athymic immunoincompetent rats after implantation with cultured thymic fragments (CIF) under the kidney capsule, with special emphasis on the settlement of lymphocytes and non-lymphnid RTl class II elements. At 2 weeks after grafting, tissue under the kidney capsule comprises strands of keratin-positive epithelial cells from the graft, without immigrant cells. At 3 weeks, the CTF graft is populated with lymphoeytes and with non-lymphoid RTl class II-positive cells expressing the recipient haplotype (allogeneic combinations). Part of these cells bear determinants recognized by an anti-rat dendritic cell antibody. At 4 weeks the graft exhibits a completely restored thymic architecture. Al the periphery, the first indications of T-cell competence generated after CTF implantation are observed 6 weeks after implantation. At 18 weeks. the peripheral thymus-dependent immune system is almost completely developed. This includes in vitro alloreactivity, even to the donor RTl haplotype of the graft. But skin grafts of the allogeneic CTF donor haplotype are not rejected. Thus, a state of in vivo tolerance is induced under the influence of grafted epithelium, which is not due to a specific deletion of alloreactive cells. We conclude that CTF regain their original thymic architecture between 2 and 4 weeks after implantation in (allogeneic) athymic nude recipients, and that only after this restoration does peripheral thymus-dependent immune competence start to develop.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 21 (1985), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We have extended our previous siudy of induction of T-lymphocyte immunocompetence in athymic nude rats by cultured epithelium (CTE) of syngencic urigin to that by CTE of allogeneic origin. Immune responsiveness (IgG-class antibody und delayed-type hypersensi-liviiy) after ovalbumin immunization is detectable by -1–6 weeks after transplantation. However, the antibody appears at a slower rate when compared with heterozygous immunocompeient littermates. Seven weeks after transplantation phytohaemagglutinm responsiveness of spleen cells is detectable, and in‘Independent areas of lymphoid organs lymphocytes with helper and non-helper T-cell phcnotype are presenl, bul at lower levels than those in heterozygous immunocompetenl littermates. Levels comparable to that of immunocompeient rals are reached about 20 weeks after transplantation. Since CTE contains thymocytes. control experiments consisted of transplantation with high numbers of allogeneic freshly isolated thymocytes in alhymic nude ratv These animals showed IgG-class antibody formation after ovalbumin immunization, but at lower levels than CTE-treated rats, and were almost negative in T-cell immunocompetence assessed in the other assays. We conclude that CTE of allogeneic origin induces T-eell immunocompetence in athymic nude rats to the level of heterozygous immunocompeteni littermates. This study adds to the rationale of CTE transplantation applied in treatment of thymic dysfunction.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 24 (1986), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We studied the thymus-dependent immune system in congenitally athymic (nude) rats of the WAG (RT-1a) strain, at the ages of 2, 3, 5, 9 and 17 months. This included the histology of spleen, lymph nodes, and Peyer's patches, immunohistochemistry on tissue sections, and immunocytology on cell suspensions using a panel of monoclonal antibodies to T-lymphocyte subpopulations. in vitro mitogen responsiveness, and in vivo responsiveness to ovalbumin immunization. The results were compared with those in euthymic immunocompetent litter-mates of the same age. The cell marker analysis, especially in nude animals, was hampered by the staining of non-T cells by some of the antibodies (staining of putative macrophages, natural killer cells, cells of H-lymphocyte lineage, and of myeloid lineage I. Despite this, with age an increase in cells with these markers was observed; for instance, in spleen suspensions, cells labelled by the pan-I reagent MRCOX-19 increased from 5% at 2 months to 19% at 17 months (value in euthymic animals 34%). In the other assays too a gradual increase of T-cell reactivity with age was observed, from almost absent in 2- and 3-month-old nude rats to values in 17-month-old animals of about hall the level round in euthymic rats. However, none of the nude animals responded to ovalbumin immunization. These results indicate that in nude animals processes occur which compensate for the absent intrathymic T-cell generation. This applies in particular to changes in T-cell phenotype and mitogen responsiveness, but not to antigen responsiveness.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Cultured thymic fragments (CTF) from WAG/CPB(RTU and DA/01a (RT1a rats were prepared in the presence or absence of 2′ deoxyguanosine or cyclosporine A, and subsequently transplanted under the kidney capsule of congenitally athymic and euthymic WAG CPB recipients. The rationale of the culture supplements was that these may affect the disappearance of medullary dendritic cells, with subsequent induction of allotolerance. However, the immunohistology of the CTF showed more RTI class II-positive cells than keratin-positive cells, indicative of the maintenance of dendritic cells. Grafts in athymic animals showed the recovery of the original thymic architecture within 6 weeks utter transplantation. The influx of host-derived lymphocytes was accompanied by an influx of dendritic cells in the deculla-like area and macrophages in the cortex. A similar recovery was observed for syngeneic CTF in euthymic recipients. In addition lymphocytic infiltration was seen in the connective tissue surrounding the epithelial areas. Allogeneic grafts in euthymic animals were rejected within 3 weeks after transplantation. This outcome of the transplanted CTF under different conditions was not affected by the supplementation of the thymic culture before transplantation with 2′ deoxyguanosine or cyclosporine A.We conclude that there is no tolerance induction after transplantation in euthymic allogeneic rats of CTF prepared in the presence of 2′ deoxyguanosine. This conclusion is in contrast to date in the mouse, which may be explained by the maintenance of dendrite cells during culture. A chimaeric state of donor-derived epithelium and host-derived dendritic cells is obtained by transplantation of allografts in arthymic rats.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 18 (1983), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The combination of centrifugal elutriation as an efficient and reproducible method to separate thymocytes by size, micromethods to assess purine interconversion enzymes, and assessment of purine (deoxy) nucleoside inhibition of mitogen responses enabled us to study purine metabolism at the intrathymic level. Out of six fractions, four (nos. 3–6), containing medium-and large-sized lymphocytes, showed a proliferative response after stimulation with phytohaemagglutinin (PHA). In fractions 1–6 the number of cells with an immature immunological phenotype gradually decreased, and cells with the phenotype of mature cells gradually increased. The enzyme activity ratio of adenosine deaminase to purine nucleoside phosphorylase gradually decreased from 21 in fraction 1 to 7 in the last fraction (blood T-cell value, 0.7). We conclude that this enzyme activity ratio is a useful marker for intrathymic T-cell maturation stages. In PHA-responsive cell fractions (3–6), the sensitivity to inhibition of the PHA response by (deoxy) adenosine and deoxyguanosine was inversely related to the enzyme activity ratio of ecto-5′-nucleotidase to deoxycytidine kinase. These findings are compatible with the hypothesis that intracellular concentrations of phosphorylated (deoxy) nucleosides are related to this inhibition. We conclude that the differences in purine metabolism among the various (mitogen-responsive) human thymocyte fractions are related to lymphoid cell function. Since the number of cells contributing to the enzyme activities and the number of cells contributing to the proliferative response (about 15% of unseparated cells) differ considerably, it is not possible to evaluate enzyme activities in unseparated thymocytes in terms of relationships between purine metabolism and lymphocyte function.
    Type of Medium: Electronic Resource
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