Tolerogenic maturation of liver sinusoidal endothelial cells promotes B7-homolog 1-dependent CD8+ T cell tolerance
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Tolerogenic maturation of liver sinusoidal endothelial cells promotes B7-homolog 1-dependent CD8+ T cell tolerance. / Diehl, Linda; Schurich, Anna; Grochtmann, Regina; Hegenbarth, Silke; Chen, Lieping; Knolle, Percy A.
in: HEPATOLOGY, Jahrgang 47, Nr. 1, 01.2008, S. 296-305.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Tolerogenic maturation of liver sinusoidal endothelial cells promotes B7-homolog 1-dependent CD8+ T cell tolerance
AU - Diehl, Linda
AU - Schurich, Anna
AU - Grochtmann, Regina
AU - Hegenbarth, Silke
AU - Chen, Lieping
AU - Knolle, Percy A
PY - 2008/1
Y1 - 2008/1
N2 - UNLABELLED: Liver sinusoidal endothelial cells (LSEC) are unique organ-resident antigen-presenting cells capable of cross-presentation and subsequent tolerization of naïve CD8(+) T cells. We investigated the molecular mechanisms underlying this tolerance induction in naive CD8(+) T cells. MHC class I-restricted antigen presentation by LSEC led to initial stimulation of naïve CD8(+) T cells, which up-regulated CD69, CD25, CD44, and programmed death (PD)-1 and proliferated similar to dendritic cell (DC)-activated CD8(+) T cells. Importantly, cognate interaction with naïve CD8(+) T cells triggered increased expression of co-inhibitory B7-H1 but not co-stimulatory CD80/86 molecules exclusively on LSEC but not DC. This matured phenotype of B7-H1(high) CD80/86(low) was critical for induction of CD8(+) T cell tolerance by LSEC: B7-H1-deficient LSEC, that failed to interact with PD-1 on stimulated T cells, were incapable of inducing CD8(+) T cell tolerance. Moreover, increased costimulation via CD28 interfered with tolerance induction, indicating that the noninducible low expression levels of CD80/86 on LSEC supported B7-H1-dependent tolerance induction. LSEC-tolerized CD8(+) T cells had a distinctive phenotype from naïve and activated T cells with CD25(low), CD44(high), CD62L(high). They also expressed the homeostatic cytokine receptors CD127, CD122, and high levels of Bcl-2, indicating survival rather than deletion of tolerant CD8(+) T cells. On adoptive transfer into congenic animals, tolerized CD8(+) T cells failed to show specific cytotoxicity in vivo.CONCLUSION: Cognate interaction of LSEC with naïve CD8(+) T cells elicits a unique tolerogenic maturation of LSEC and permissiveness of T cells for tolerogenic signals, demonstrating that LSEC-induced tolerance is an active and dynamic process.
AB - UNLABELLED: Liver sinusoidal endothelial cells (LSEC) are unique organ-resident antigen-presenting cells capable of cross-presentation and subsequent tolerization of naïve CD8(+) T cells. We investigated the molecular mechanisms underlying this tolerance induction in naive CD8(+) T cells. MHC class I-restricted antigen presentation by LSEC led to initial stimulation of naïve CD8(+) T cells, which up-regulated CD69, CD25, CD44, and programmed death (PD)-1 and proliferated similar to dendritic cell (DC)-activated CD8(+) T cells. Importantly, cognate interaction with naïve CD8(+) T cells triggered increased expression of co-inhibitory B7-H1 but not co-stimulatory CD80/86 molecules exclusively on LSEC but not DC. This matured phenotype of B7-H1(high) CD80/86(low) was critical for induction of CD8(+) T cell tolerance by LSEC: B7-H1-deficient LSEC, that failed to interact with PD-1 on stimulated T cells, were incapable of inducing CD8(+) T cell tolerance. Moreover, increased costimulation via CD28 interfered with tolerance induction, indicating that the noninducible low expression levels of CD80/86 on LSEC supported B7-H1-dependent tolerance induction. LSEC-tolerized CD8(+) T cells had a distinctive phenotype from naïve and activated T cells with CD25(low), CD44(high), CD62L(high). They also expressed the homeostatic cytokine receptors CD127, CD122, and high levels of Bcl-2, indicating survival rather than deletion of tolerant CD8(+) T cells. On adoptive transfer into congenic animals, tolerized CD8(+) T cells failed to show specific cytotoxicity in vivo.CONCLUSION: Cognate interaction of LSEC with naïve CD8(+) T cells elicits a unique tolerogenic maturation of LSEC and permissiveness of T cells for tolerogenic signals, demonstrating that LSEC-induced tolerance is an active and dynamic process.
KW - Animals
KW - Antigens, CD
KW - Antigens, CD274
KW - Apoptosis Regulatory Proteins
KW - CD8-Positive T-Lymphocytes
KW - Dendritic Cells
KW - Endothelial Cells
KW - Gene Expression
KW - Immune Tolerance
KW - Liver
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Phenotype
KW - Programmed Cell Death 1 Receptor
KW - Signal Transduction
U2 - 10.1002/hep.21965
DO - 10.1002/hep.21965
M3 - SCORING: Journal article
C2 - 17975811
VL - 47
SP - 296
EP - 305
JO - HEPATOLOGY
JF - HEPATOLOGY
SN - 0270-9139
IS - 1
ER -