Interleukin 15 is produced by endothelial cells and increases the transendothelial migration of T cells In vitro and in the SCID mouse-human rheumatoid arthritis model In vivo.
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.
Oppenheimer-Marks
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N
Rheumatic Diseases Division of the Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas, Texas 75235-8577, USA. mmarks@mednet.swmed.edu
Brezinschek
R I
RI
Mohamadzadeh
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M
Vita
R
R
Lipsky
P E
PE
D019264:Adoptive Transfer; D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000276:immunology* / Q000378:metabolism*; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D019409:Interleukin-15 / Q000276:immunology* / Q000378:metabolism*; D037181:Lectins, C-Type; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D012333:RNA, Messenger / Q000378:metabolism; D013583:Synovial Membrane / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016378:Tissue Transplantation; D014471:Umbilical Veins / Q000166:cytology / Q000276:immunology; D000099192:CD69 Antigens
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018799:Intercellular Adhesion Molecule-1; D019409:Interleukin-15; D037181:Lectins, C-Type; D016169:Lymphocyte Function-Associated Antigen-1; D012333:RNA, Messenger; D000099192:CD69 Antigens