Abstract
The capacity of endothelial cells (EC) to produce IL-15 and the capacity of IL-15 to influence transendothelial migration of T cells was examined. Human umbilical vein endothelial cells expressed both IL-15 mRNA and protein. Moreover, endothelial-derived IL-15 enhanced transendothelial migration of T cells as evidenced by the inhibition of this process by blocking monoclonal antibodies to IL-15. IL-15 enhanced transendothelial migration of T cells by activating the binding capacity of the integrin adhesion molecule LFA-1 (CD11a/CD18) and also increased T cell motility. In addition, IL-15 induced expression of the early activation molecule CD69. The importance of IL-15 in regulating migration of T cells in vivo was documented by its capacity to enhance accumulation of adoptively transferred human T cells in rheumatoid arthritis synovial tissue engrafted into immune deficient SCID mice. These results demonstrate that EC produce IL-15 and imply that endothelial IL-15 plays a critical role in stimulation of T cells to extravasate into inflammatory tissue.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adoptive Transfer
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Animals
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Antibodies, Blocking / immunology
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Antibodies, Monoclonal / immunology
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Antigens, CD / metabolism
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Antigens, Differentiation, T-Lymphocyte / metabolism
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Arthritis, Rheumatoid / immunology*
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Arthritis, Rheumatoid / metabolism
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Cell Adhesion / immunology
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Cell Movement / immunology
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Cells, Cultured
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Endothelium, Vascular / immunology*
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Endothelium, Vascular / metabolism*
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Flow Cytometry
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Fluorescent Antibody Technique, Indirect
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Humans
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Immunohistochemistry
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Inflammation / immunology
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Inflammation / metabolism
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Intercellular Adhesion Molecule-1 / metabolism
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Interleukin-15 / immunology*
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Interleukin-15 / metabolism*
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Lectins, C-Type
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Lymphocyte Function-Associated Antigen-1 / metabolism
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Mice
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Mice, SCID
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RNA, Messenger / metabolism
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Synovial Membrane / immunology
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Synovial Membrane / metabolism
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Synovial Membrane / transplantation
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T-Lymphocytes / cytology
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism
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Tissue Transplantation
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Umbilical Veins / cytology
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Umbilical Veins / immunology
Substances
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Antibodies, Blocking
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Antibodies, Monoclonal
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Antigens, CD
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Antigens, Differentiation, T-Lymphocyte
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CD69 antigen
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Interleukin-15
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Lectins, C-Type
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Lymphocyte Function-Associated Antigen-1
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RNA, Messenger
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Intercellular Adhesion Molecule-1