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Activated Murine Endothelial Cells Have Reduced Immunogenicity for CD8⁺ T Cells: A Mechanism of Immunoregulation?¹

Federica M. Marelli-Berg^2,*, Diane Scott, Istvan Bartok, Emma Peek^*, Julian Dyson and Robert I. Lechler^*

^* Department of Immunology, Imperial College School of Medicine and Medical Research Council Clinical Science Center, Hammersmith Hospital, London, United Kingdom

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- 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-K^k-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-K^k 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.

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