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Immunol Rev. 1990 Oct;117:85-102.

The endothelial cell as a regulator of T-cell function.

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Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.


These studies have analyzed the antigen-presenting capacities of EC. EC can transcribe, translate and express MHC class II molecules in response to IFN-gamma as well as express class I molecules. The class II dimeric structure is functional, in that allospecific CTL can efficiently kill IFN-gamma-treated EC or fibroblasts, an outcome that can be blocked by antibody to non-polymorphic regions of the class II molecule. Moreover, EC can present antigen in an MHC-restricted manner to resting T cells as well as to antigen-specific cloned T-cell lines. This ability to stimulate primary as well as secondary responses has been further confirmed by experiments using purified populations of naive and memory T cells. In this regard, EC differ from fibroblasts and other non-immune cell types in that they possess costimulator activities necessary for activation of resting T cells. As the local concentration of IL-2 has been shown to be critical in determining the fate of T cells--whether they become activated or anergic--we have investigated the ability of EC to modulate T-cell IL-2 production, believing that this may underlie their ability to act as costimulatory cells. Using PHA-stimulated peripheral blood mononuclear cells or purified CD4+ T cells we have found that EC can augment IL-2 production, typically by 3- to 8-fold. This increased IL-2 production is functional as OKT3-stimulated or sub-optimally PHA-stimulated T cells proliferate more in the presence of EC than in their absence. The major pathway by which EC augment T-cell IL-2 production is cell contact-dependent and involves the CD2:LFA-3 ligand pair. However, use of blocking mAb to CD2 and LFA-3, of PI-LFA-3, and of the immunosuppressive drug CsA has allowed us to reveal the presence of a second signalling pathway. This pathway confers a certain degree of CsA resistance on T cells, but the ligands involved have not yet been identified. We do not find a role for CD28, LFA-1:ICAM-1, VLA-4:VCAM-1 or CD44 in this system. Augmentation is independent of EC metabolism or soluble factors, as fixed cells are almost as efficient as living cells. Similar mechanisms seem also to be involved in more physiological settings, such as alloresponses. Here, proliferation can be blocked by antibodies to CD2 or LFA-3, presumably by blocking of augmented IL-2 production.(ABSTRACT TRUNCATED AT 400 WORDS)

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