Endotoxin activates T cell interferon-gamma secretion in the presence of endothelium.
T lymphocytes (T cells) and their secreted lymphokine interferon-gamma (IFN-gamma) play important mediator roles in endotoxin-induced inflammation. We sought to explore the necessary conditions for and degree of LPS-induced T cell activation for IFN-gamma secretion in a human syngeneic microvascular endothelial-T cell coculture system. Human peripheral blood T cells, with or without monocytes, were cocultured in the presence or absence of a syngeneic human adipose microvascular endothelial cell (HAMVEC) monolayer. Cocultures were stimulated with LPS (1 microgram/ml) and 3-day coculture supernatants assayed for IFN-gamma and IL-2 by ELISA. In the absence of HAMVEC, LPS-induced T cell activation for IFN-gamma secretion was only minimally demonstrated in the presence of monocytes. However, in the presence of HAMVEC, LPS activated T cells for IFN-gamma secretion in the absence of monocytes and markedly augmented the response in the presence of monocytes. A subset of donor cocultures showed no IFN-gamma response to LPS. IL-2 was not secreted as part of the LPS-induced T cell activation response. Our data support a hypothesis that endothelium serves as an accessory cell for T cell IFN-gamma secretion in endotoxin-induced inflammation. T cell-endothelial interactions may play a crucial role in promoting T cell activation during LPS-induced inflammation.
Tennenberg
S D
SD
Department of Surgery, Allen Park Veterans Affairs Medical Center, Wayne State University School of Medicine, Detroit, Michigan 48101, USA.
Weller
J J
JJ
D000273:Adipose Tissue / Q000098:blood supply; D000328:Adult; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D004731:Endotoxins / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000378:metabolism; D007376:Interleukin-2 / Q000096:biosynthesis; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008833:Microcirculation; D009000:Monocytes / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013997:Time Factors
D004731:Endotoxins; D007376:Interleukin-2; D008070:Lipopolysaccharides; D007371:Interferon-gamma