Costimulator deficient antigen presentation by an endothelial cell line induces a nonproliferative T cell activation response without anergy.

Abstract

SRmmaryThe ability of endothelial cells to activate helper T (Th) cells by antigen presentation was studied using the murine endothelial cell line SVEC4-10 and antigen-specific murine T cell clones. SEVEC4-10 cells constitutively express vascular cell adhesion molecule 1 but not intercellular adhesion molecule 1. Interferon 7 (IFN-7) treatment of these cells induced class II major histocompatibility complex (MHC) expression and antigen-presenting capabilities, but did not alter surface integrin expression. IFN-7-treated SVEC4-10 cells were competent at mediating antigen-dependent cytokine production and proliferation ofa Th2 done. In contrast, endothelial antigen presentation to Thl cells did not stimulate T cell proliferation. The addition of MHC mismatched spleen cells as a source ofcostimulatory molecules resulted in the ability of the endothelial cells to stimulate Thl cell proliferation in an antigen-spedfic manner. The failure of the endothelial cell line alone to support Thl cell proliferation correlated with the failure to stimulate interleukin 2 (IL-2) gene expression. T cell exposure to the endothelial cells plus antigen resulted in upregnlation of IL-2 receptors and an enhanced response to subsequent antigen presentation by splenic antigenpresenting cells. Despite the lack of functional costimulators for IL-2 expression, antigen presentation by the endothelial cell line did not induce Thl cell anergy, indicating that costimulator deficiency for IL-2 expression is not obligatorily linked to anergy induction. Thus, endothelial cells are capable of presenting antigens to helper T lymphocytes, but stimulate only partial T cell responses. These partial responses may serve to selectively stimulate transmigration of antigen-specific T cells and may enhance functional responses upon subsequent, extravascular antigen exposure.

Eimeria bovis infection enhances adhesion of peripheral blood mononuclear cells to and their transmigration through an infected bovine endothelial cell monolayer in vitro

“…show protective cytotoxic reaction predominantly affecting very early stages (see Shi et al 2001). In this concern, it has to be considered that endothelial cell in principle, are able to display antigenpresenting function and to activate CD4 + and CD8 + T cells in an antigen-dependent manner (Pober and Cotran 1991;St Louis et al 1993;Epperson and Pober 1994;Ma and Pober 1998;Rodig et al 2003).…”

Identification of thyroid stimulating hormone receptor-specific T cells in Graves' disease thyroid using autoantigen-transfected Epstein-Barr virus-transformed B cell lines.

“…These results are difficult to reconcile with the capacity of these clones to produce IL-2 when exposed to potent stimuli like OKT3 and PMA (Table I). That they may synthesize only small quantities of IL-2 in vivo, or after suboptimal stimulation with fixed EBVL in vitro, cannot be excluded (26).…”

“…The ability of transfected EBVL, in this and previous studies, to effectively present endogenously synthesized TPO and TSHR supports the concept that cells expressing surface autoantigen (such as TEC) could act as APC, as long as they also possess appropriate costimulatory properties. Since GD thyroid contains dendritic cells, it is also conceivable that the primary autoimmune response could be initiated either by professional APC presenting locally liberated antigen or by TEC assisted by third party "bystander" APC delivering the necessary costimuli (26). Suboptimal activation of naive T cells by TEC might lead not to complete T cell inactivation or deletion but to alteration of the Thl /Th2 balance in their antigen-specific response (26,49).…”

“…Since GD thyroid contains dendritic cells, it is also conceivable that the primary autoimmune response could be initiated either by professional APC presenting locally liberated antigen or by TEC assisted by third party "bystander" APC delivering the necessary costimuli (26). Suboptimal activation of naive T cells by TEC might lead not to complete T cell inactivation or deletion but to alteration of the Thl /Th2 balance in their antigen-specific response (26,49).…”

ICAM‐2 Provides a Costimulatory Signal for T Cell Stimulation by Allogeneic Class II MHC

“…Therefore, those cells may function in antigen presentation under certain conditions. Indeed, the capacity of an endothelial cell line to function as an APC has been reported [36]. In addition, demonstration that the two required signals for T cell activation may be delivered by two separate cells also raises the possibility that CAMs may not be an absolute requirement on an APC.…”