Priming of CD8+ T cell responses by pathogens typically depends on CD70-mediated interactions with dendritic cells.
The CD27/CD70-interaction has been shown to provide a costimulatory and survival signal for T cells in vitro and in vivo. Recently, CD70 expression by DC was found to be important for the priming of CD8+ T cells. We show here that blocking CD70 interactions has a significant impact on priming of CD8+ T cell responses by vaccinia virus (VV), Listeria monocytogenes and vesicular stomatitis virus (VSV) in mice. However, the priming of specific CD8+ T cells upon infection with lymphocytic choriomeningitis virus (LCMV) was only marginally reduced by CD70-blockade. Blocking of CD70 prevented CD8+ T cell priming in DIETER mice, a model in which presentation of LCMV-derived epitopes can be induced selectively in dendritic cells (DC). In contrast, CD70-CD27 interactions were not important for the priming of VSV-specific CD4+ T cells or class switch of neutralizing antibodies. As we show that priming of CD8+ T cells by the pathogens used here is dependent on antigen presentation by DC and that infection results in up-regulation of CD70 on DC, we conclude that CD70 expression on DC plays an important role in the priming of CD8+ T cells by pathogens. Moreover, the lack of CD70 cannot be completely compensated for by other costimulatory molecules.
Schildknecht
Anita
A
Institute of Experimental Immunology, Zurich, Switzerland.
Miescher
Iris
I
Yagita
Hideo
H
van den Broek
Maries
M
D000595:Amino Acid Sequence; D000818:Animals; D053282:CD27 Ligand / Q000096:biosynthesis / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D008089:Listeria monocytogenes / Q000276:immunology; D008216:Lymphocytic Choriomeningitis / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D014709:Vero Cells; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology
D053282:CD27 Ligand; D018984:Epitopes, T-Lymphocyte