TY - JOUR
T1 - B7-H1 on Hepatocytes Facilitates Priming of Specific CD8 T Cells But Limits the Specific Recall of Primed Responses
AU - Wahl, Christian
AU - Bochtler, Petra
AU - Chen, Lieping
AU - Schirmbeck, Reinhold
AU - Reimann, Jörg
PY - 2008/9
Y1 - 2008/9
N2 - Background & Aims: The requirement for costimulation of CD8 T-cell priming and restimulation by nonprofessional antigen-presenting cells is unresolved. Here, we investigated whether B7-H1 (CD274, PD-L1) on hepatocytes (HC) is involved in the specific activation of naive CD8 T cells or activated CD8 T blasts. Methods: Naive or activated CD8 T cells from transgenic OT-I mice were primed/restimulated by peptide-pulsed HC, and their proliferation and effector response were determined. We used blocking monoclonal antibodies against B7-H1 and HC from B7-H1-deficient mice to assign a costimulatory or coinhibitory role to B7-H1 for CD8 T-cell priming/restimulation. Results: Blockade of B7-H1 on HC down modulated interferon (IFN)-γ production and proliferation of HC-primed CD8 T cells, indicating a costimulatory role for B7-H1 in priming CD8 T cells. In contrast, the PD-1/B7-H1 interaction inhibited proliferation and interferon-γ release of effector/memory CD8 T blasts specifically restimulated by peptide-pulsed HC. Conclusions: B7-H1 differentially modulates the different stages of the specific CD8 T-cell response triggered by HC, and, whereas it costimulates priming and cytokine responses of naive CD8 T cells, it coinhibits their specific local recall of effector cytokine responses. The interaction of CD8 T cells with B7-H1+ HC can thus fine-tune proliferative and effector responses of specific CD8 T cells reacting locally to nonprofessional antigen-presenting cells infected with hepatotropic agents.
AB - Background & Aims: The requirement for costimulation of CD8 T-cell priming and restimulation by nonprofessional antigen-presenting cells is unresolved. Here, we investigated whether B7-H1 (CD274, PD-L1) on hepatocytes (HC) is involved in the specific activation of naive CD8 T cells or activated CD8 T blasts. Methods: Naive or activated CD8 T cells from transgenic OT-I mice were primed/restimulated by peptide-pulsed HC, and their proliferation and effector response were determined. We used blocking monoclonal antibodies against B7-H1 and HC from B7-H1-deficient mice to assign a costimulatory or coinhibitory role to B7-H1 for CD8 T-cell priming/restimulation. Results: Blockade of B7-H1 on HC down modulated interferon (IFN)-γ production and proliferation of HC-primed CD8 T cells, indicating a costimulatory role for B7-H1 in priming CD8 T cells. In contrast, the PD-1/B7-H1 interaction inhibited proliferation and interferon-γ release of effector/memory CD8 T blasts specifically restimulated by peptide-pulsed HC. Conclusions: B7-H1 differentially modulates the different stages of the specific CD8 T-cell response triggered by HC, and, whereas it costimulates priming and cytokine responses of naive CD8 T cells, it coinhibits their specific local recall of effector cytokine responses. The interaction of CD8 T cells with B7-H1+ HC can thus fine-tune proliferative and effector responses of specific CD8 T cells reacting locally to nonprofessional antigen-presenting cells infected with hepatotropic agents.
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U2 - 10.1053/j.gastro.2008.05.076
DO - 10.1053/j.gastro.2008.05.076
M3 - Article
C2 - 18621049
AN - SCOPUS:51249119868
SN - 0016-5085
VL - 135
SP - 980
EP - 988
JO - Gastroenterology
JF - Gastroenterology
IS - 3
ER -