Activated Murine Endothelial Cells Have Reduced Immunogenicity for CD8+ T Cells: A Mechanism of Immunoregulation?

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Abstract
The immunogenic properties of primary cultures of murine lung microvascular endothelial cells (EC) were analyzed. Resting endothelial cells were found to constitutively express low levels of MHC class I and CD80 molecules. IFN-γ treatment of EC resulted in a marked up-regulation of MHC class I, but no change was observed in the level of CD80 expression. No CD86 molecules were detectable under either condition. The ability of peptide-pulsed EC to induce the proliferation of either the HY-specific, H2-Kk-restricted CD8+ T cell clone (C6) or C6 TCR-transgenic naive CD8+ T cells was analyzed. Resting T cells were stimulated to divide by quiescent peptide-prepulsed EC, while peptide-pulsed, cytokine-activated EC lost the ability to induce T cell division. Furthermore, Ag presentation by cytokine-activated EC induced CD8+ T cell hyporesponsiveness. The immunogenicity of activated EC could be restored by adding nonsaturating concentrations of anti-H2-Kk Ab in the presence of an optimal concentration of cognate peptide. This is consistent with the suggestion that the ratio of TCR engagement to costimulation determines the outcome of T cell recognition. In contrast, activated peptide-pulsed EC were killed more efficiently by fully differentiated effector CD8+ T cells. Finally, evidence is provided that Ag recognition of EC can profoundly affect the transendothelial migration of CD8+ T cells. Taken together, these results suggest that EC immunogenicity is regulated in a manner that contributes to peripheral tolerance.