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

TY - JOUR

T1 - Activated murine endothelial cells have reduced immunogenicity for CD8+ T cells: a mechanism of immunoregulation?

AU - Marelli-Berg, F M

AU - Scott, D

AU - Bartok, I

AU - Peek, E

AU - Dyson, J

AU - Lechler, R I

PY - 2000/10/15

Y1 - 2000/10/15

N2 - 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-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 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.

AB - 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-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 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.

M3 - Article

SN - 1550-6606

VL - 165

SP - 4182

EP - 4189

JO - Journal of Immunology

JF - Journal of Immunology

IS - 8

ER -