Endotoxin Activates T Cell Interferon-γ Secretion in the Presence of Endothelium

Abstract

T lymphocytes (T cells) and their secreted lymphokine interferon-γ (IFN-γ) 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-γ 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 μg/ml) and 3-day coculture supernatants assayed for IFN-γ and IL-2 by ELISA. In the absence of HAMVEC, LPS-induced T cell activation for IFN-γ secretion was only minimally demonstrated in the presence of monocytes. However, in the presence of HAMVEC, LPS activated T cells for IFN-γ secretion in the absence of monocytes and markedly augmented the response in the presence of monocytes. A subset of donor cocultures showed no IFN-γ 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-γ secretion in endotoxin-induced inflammation. T cell-endothelial interactions may play a crucial role in promoting T cell activation during LPS-induced inflammation.