COSTIMULATOR DEFICIENT ANTIGEN PRESENTATION BY AN ENDOTHELIAL-CELL LINE INDUCES A NONPROLIFERATIVE T-CELL ACTIVATION RESPONSE WITHOUT ANERGY

The ability of endothelial cells to activate helper T (Th) cells by an tigen presentation was studied using the murine endothelial cell line SVEC4-10 and antigen-specific murine T cell clones. SEVEC4-10 cells co nstitutively express vascular cell adhesion molecule 1 but not interce llular adhesion molecule 1. Interferon gamma (IFN-gamma) treatment of these cells induced class II major histocompatibility complex (MHC) ex pression and antigen-presenting capabilities, but did not alter surfac e integrin expression. IFN-gamma-treated SVEC4-10 cells were competent at mediating antigen-dependent cytokine production and proliferation of a Th2 clone. In contrast, endothelial antigen presentation to Th1 c ells did not stimulate T cell proliferation. The addition of MHC misma tched spleen cells as a source of costimulatory molecules resulted in the ability of the endothelial cells to stimulate Th1 cell proliferati on in an antigen-specific manner. The failure of the endothelial cell line alone to support Th1 cell proliferation correlated with the failu re to stimulate interleukin 2 (IL-2) gene expression. T cell exposure to the endothelial cells plus antigen resulted in upregulation of IL-2 receptors and an enhanced response to subsequent antigen presentation by splenic antigen-presenting cells. Despite the lack of functional c ostimulators for IL-2 expression, antigen presentation by the endothel ial cell line did not induce Th1 cell anergy, indicating that costimul ator deficiency for IL-2 expression is not obligatorily linked to aner gy induction. Thus, endothelial cells are capable of presenting antige ns to helper T lymphocytes, but stimulate only partial T cell response s. These partial responses may serve to selectively stimulate transmig ration of antigen-specific T cells and may enhance functional response s upon subsequent, extravascular antigen exposure.