Dendritic cells enriched from swine thymus co-express CD1, CD2 and major histocompatibility complex class II and actively stimulate alloreactive T lymphocytes.
Initial characterization and partial purification of thymic dendritic cells (DC) from miniature swine were carried out with the ultimate goal of using these cells to induce transplantation tolerance in this preclinical animal model. Immunohistochemical analysis of swine thymic tissue sections has shown DC to be large cells located in the medullary and the cortico-medullary regions as evidenced by the presence of surrounding Hassal bodies. These cells exhibit membrane processes and express the CD1, granulocyte/macrophage (G/M), and major histocompatibility complex (MHC) class II surface antigens, as well as the S100 cytosolic and nuclear markers found in humans to be specific for DC. Dendritic cells were purified from thymi following collagenase treatment, Percoll gradient centrifugation, and adhesion steps to plastic. Cells similar in morphology and phenotype to those described in tissue sections were detected in the lighter density layers of the gradient and represented 0.02% of the starting cell number. Removal of plastic nonadherent cells showed enrichment levels similar to those reported for murine and human DC. Two-colour flow cytometric analysis of purified pig DC identified these cells as MHC class IIhi, CD1+, CD2+, and G/M+. The dendritic nature of these cells was confirmed by their potent ability to stimulate alloreactive T lymphocytes. Modification of porcine thymic DC by transfer of allogeneic MHC genes and reinjection into the DC donor should permit testing of the role of this DC subset in the induction of transplantation tolerance.
Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, MGH-East, Bldg 149-9019, 13th Street, Boston, MA 01229, USA.
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Salmon
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Johnson
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Germana
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Haller
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Sachs
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Leguern
D000818:Animals; D018949:Antigens, CD1 / Q000378:metabolism*; D018801:CD2 Antigens / Q000378:metabolism*; D002448:Cell Adhesion; D002469:Cell Separation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007519:Isoantigens; D007959:Lymphocyte Culture Test, Mixed; D013552:Swine; D013556:Swine, Miniature; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology*
D018949:Antigens, CD1; D018801:CD2 Antigens; D000949:Histocompatibility Antigens Class II; D007519:Isoantigens