First Author | Wahl C | Year | 2008 |
Journal | Gastroenterology | Volume | 135 |
Issue | 3 | Pages | 980-8 |
PubMed ID | 18621049 | Mgi Jnum | J:141857 |
Mgi Id | MGI:3819902 | Doi | 10.1053/j.gastro.2008.05.076 |
Citation | Wahl C, et al. (2008) B7-H1 on hepatocytes facilitates priming of specific CD8 T cells but limits the specific recall of primed responses. Gastroenterology 135(3):980-8 |
abstractText | 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)-gamma 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-gamma 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. |