In vitro experiments have shown that endothelial cells can function as antigen-presenting cells to CD4+ T lymphocytes. The studies presented here address the question of whether naive 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 stimulated in vitro with 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 naive CD4+ T cells. When costimulatory signals were provided in trans by the addition of MHC-mismatched mouse spleen cells, activation of naive 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 naive T cells. Furthermore, the mouse lung endothelium constitutively expresses B7-1, and therefore, the inability of endothelium to stimulate naive 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.
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