Endothelial Antigen Presentation: Stimulation of Previously Activated but Not Naı̈ve TCR-Transgenic Mouse T Cells

In vitroexperiments have shown that endothelial cells can function as antigen-presenting cells to CD4+T lymphocytes. The studies presented here address the question of whether naı̈ve versus previously activated CD4+helper T cells differ in their responses to endothelial antigen presentation. TCR-transgenic mice were used as a source of naive T cells of defined antigen specificity. These cells were stimulatedin vitrowith antigen and splenic antigen-presenting cells to generate populations of T lymphocytes with a previously activated/memory phenotype. Two different types of mouse endothelial cells were used as antigen-presenting cells, including the SVEC4-10 line derived from lymph node endothelium and primary murine pulmonary microvascular endothelium. Monolayer cultures of both types of endothelium were capable of antigen-dependent stimulation of previously activated TCR-transgenic CD4+cells. In contrast, neither endothelial type could activate naı̈ve CD4+T cells. When costimulatory signals were providedin transby the addition of MHC-mismatched mouse spleen cells, activation of naı̈ve T cells by endothelial antigen presentation could be demonstrated. The expression of ICAM-1 or VCAM-1 on the endothelial cells was not sufficient to activate naı̈ve T cells. Furthermore, the mouse lung endothelium constitutively expresses B7-1, and therefore, the inability of endothelium to stimulate naı̈ve T cells could not be attributed to a lack of CD28-ligands. These studies suggest that the potential role of endothelial antigen presentation in immune responses is restricted to promoting responses by T cells which have previously encountered antigen presented by other antigen-presenting cells.