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Cartilage formed by syngeneic rat chondrocytes in joint surface defects is rejected in animals sensitized with allogeneic chondrocytes: involvement of the synovial lining

100%
Moskalewski S., Osiecka-Iwan A., Hyc A., Niderla J.
Archivum Immunologiae et Therapiae Experimentalis
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2005
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vol. 53
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issue 2
159-168
EN
The aim of the study was to discover the mechanism of rejection of chondrocyte transplants introduced into articular cartilage defects. Chondrocytes from 3?5-day-old Lewis or WAG rats were liberated by enzymatic digesand tion from articular-epiphyseal cartilage complexes and implanted into defects made in the subpatellar region of the femur condyle of naive Lewis rats. Syngeneic transplants were also done after sensitization of the recipients with allogeneic chondrocytes injected intramuscularly. The transplants and synovial membrane were studied in periodate-lysineparaformaldehyde- fixed material with antibodies against B lymphocytes, CD4+ and CD8+ cells, NK cells, and macrophages. For detection of humoral response, chondrocyte lysates were subjected to protein electrophoresis and Western blotting with sera from the transplant recipients. Cartilage produced in intracartilaginous transplants of syngeneic chondrocytes did not show any signs of rejection. CD8+ lymphocytes and macrophages accumulated in the vicinity of cartilage produced by similar transplants in animals sensitized with intramuscular transplants of allogeneic WAG chondrocytes or bearing transplants of allogeneic WAG chondrocytes. CD8+ cells penetrated into the peripheral part of the cartilage, while macrophages advanced much more deeply. No specific anti-chondrocyte antibody was detected. The synovium from rats bearing intracartilaginous transplants of allogeneic chondrocytes or syngeneic chondrocytes after sensitization contained macrophages and CD8+ cells. The rejection of cartilage formed by syngeneic chondrocyte transplants in sensitized animals argues in favor of a chondrocyte-specific antigen expression. The involvement of the synovial membrane during transplant rejection suggests that it should be included in observations of the behavior of chondrocyte transplants introduced into articular cartilage.
2

A direct comparison of rejection by CD8 and CD4 T cells in a transgenic model of allotransplantation

86%
Porrett P. M., Lee I. M. K., Lian M. M., Wang J., Caton A. J., Deng S., Markmann J. E., Moore D. J.
Archivum Immunologiae et Therapiae Experimentalis
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2008
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vol. 56
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issue 3
192-200
EN
Introduction: The relative contributions of CD4+ and CD8+ T cells to transplant rejection remains unknown. The authors integrated a previous model of CD4-mediated graft rejection with a complementary model of CD8-mediated rejection to directly compare the function of graft-reactive CD4+ and CD8+ lymphocytes in vivo in a model where rejection requires transgenic T cells. These studies allow direct comparison of CD4 and CD8 T cell responses to the same antigen without the confounding effects of T cell depletion or homeostatic proliferation. Materials and Methods: Clone 4 and TS1 mice possess MHC class I- and II-restricted CD8+ and CD4+ T cells, respectively, which express transgenic T cell receptors that recognize the influenza hemagglutinin antigen (HA). We compared the in vivo response of CFSE-labeled, HA-specific transgenic CD8+ and CD4+ T cells after adoptive transfer into syngeneic BALB/c mice grafted with HA-expressing skin. Results: As in the authors' CD4+ model, HA104 skin was consistently rejected by both Clone 4 mice (n=9, MST: 14.2) and by 5x105 Clone 4 lymphocytes transferred to naive BALB/c hosts that do not otherwise reject HA+ grafts. Rejection correlated with extensive proliferation of either graft-reactive T cell subset in the draining lymph nodes, and antigen-specific CD4+ and CD8+ cells acquired effector function and proliferated with similar kinetics.Conclusions: These data extend the authors' unique transgenic transplantation model to the investigation of CD8 T cell function. The initial results confirm fundamental functional similarity between the CD4 and CD8 T cell subsets and provide insight into the considerable redundancy underlying T cell mechanisms mediating allograft rejection.
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