Activated murine endothelial cells have reduced immunogenicity for CD8(+) T cells: A mechanism of immunoregulation?

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. IF N-gamma 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 molecul es were detectable under either condition. The ability of peptide-pulsed EC to induce the proliferation of either the MY-specific, H2-K-k-restricted C D8(+) T cell clone (C6) or C6 TCR-transgenic naive CD8(+) T cells was analy zed. Resting T cells were stimulated to divide by quiescent peptide-prepuls ed EC, while peptide-pulsed, cytokine-activated EC lost the ability to indu ce T cell division. Furthermore, Ag presentation by cytokine-activated EC i nduced CD8(+) T cell hyporesponsiveness. The immunogenicity of activated EC could be restored by adding nonsaturating concentrations of anti-H2-K-k Ab in the presence of an optimal concentration of cognate peptide. This is co nsistent with the suggestion that the ratio of TCR engagement to costimulat ion determines the outcome of T cell recognition. In contrast, activated pe ptide-pulsed EC were killed more efficiently by fully differentiated effect or CD8(+) T cells. Finally, evidence is provided that Ag recognition of EC can profoundly affect the transendothelial migration of CD8(+) T cells. Tak en together, these results suggest that EC immunogenicity is regulated in a manner that contributes to peripheral tolerance.