B7-H1 on hepatocytes facilitates priming of specific CD8 T cells but limits the specific recall of primed responses.
OBJECTIVE
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.
Wahl
Christian
C
Department of Internal Medicine I, University of Ulm, Ulm, Germany. christian.wahl@uni-ulm.de
Bochtler
Petra
P
Chen
Lieping
L
Schirmbeck
Reinhold
R
Reimann
Jörg
J
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D000954:Antigens, Surface / Q000032:analysis; D060890:B7-H1 Antigen; D018106:CD28 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D015536:Down-Regulation; D005260:Female; D022781:Hepatocytes / Q000276:immunology*; D007156:Immunologic Memory; D018189:Immunomagnetic Separation; D060889:Inducible T-Cell Co-Stimulator Protein; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D018106:CD28 Antigens; C556692:ICOS protein, human; C556694:Icos protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein; D007371:Interferon-gamma