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 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 gamma (IFN-gamma) treatment of these cells induced class II major histocompatibility complex (MHC) expression and antigen-presenting capabilities, but did not alter surface 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 cells did not stimulate T cell proliferation. The addition of MHC mismatched spleen cells as a source of costimulatory molecules resulted in the ability of the endothelial cells to stimulate Th1 cell proliferation in an antigen-specific manner. The failure of the endothelial cell line alone to support Th1 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 upregulation of IL-2 receptors and an enhanced response to subsequent antigen presentation by splenic antigen-presenting cells. Despite the lack of functional costimulators for IL-2 expression, antigen presentation by the endothelial cell line did not induce Th1 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.
St Louis
J D
JD
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Lederer
J A
JA
Lichtman
A H
AH
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D002460:Cell Line; D002478:Cells, Cultured; D002999:Clone Cells; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis; D007700:Kinetics; D008213:Lymphocyte Activation; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D016133:Polymerase Chain Reaction / Q000379:methods; D012313:RNA / Q000302:isolation & purification; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D007376:Interleukin-2; D011994:Recombinant Proteins; D012313:RNA; D007371:Interferon-gamma