Abstract
The CD154/CD40 interaction is an important pathway of CD4 T cell help for CD8 T cell responses. In this study, we address the role of CD70, a member of the TNF superfamily and the ligand for the T cell costimulatory receptor CD27, in CD40-mediated priming of CD8 T cells. Using an agonistic anti-CD40 mAb to mimic the CD154/CD40 interaction we demonstrate that the priming of OT-I TCR transgenic or endogenous mouse OVA-specific CD8 T cells is critically dependent on CD70/CD27 interaction. CD70 blockade inhibited CD40-mediated clonal expansion of CD8 T cells and reduced the number of memory CD8 T cells generated. Furthermore, CD70 blockade during the initial priming of CD8 T cells inhibited the ability of memory CD8 T cells to expand in response to a second encounter with Ag. Our data indicate that CD70 expression on APCs plays a key role in CD40-dependent CD8 T cell responses.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Antibodies, Blocking / pharmacology
-
Antibodies, Monoclonal / pharmacology
-
Antigen-Presenting Cells / immunology*
-
Antigen-Presenting Cells / metabolism*
-
Antigens, CD / biosynthesis
-
Antigens, CD / immunology
-
Antigens, CD / physiology*
-
CD27 Ligand
-
CD40 Antigens / immunology
-
CD40 Antigens / physiology*
-
CD8-Positive T-Lymphocytes / cytology
-
CD8-Positive T-Lymphocytes / immunology*
-
CD8-Positive T-Lymphocytes / metabolism*
-
Cell Differentiation / genetics
-
Cell Differentiation / immunology
-
Cells, Cultured
-
Dendritic Cells / immunology
-
Dendritic Cells / metabolism
-
Epitopes, T-Lymphocyte / immunology
-
Growth Inhibitors / pharmacology
-
Immunologic Memory / genetics
-
Lymphocyte Activation* / genetics
-
Lymphocyte Activation* / immunology
-
Membrane Proteins / antagonists & inhibitors
-
Membrane Proteins / biosynthesis
-
Membrane Proteins / immunology
-
Membrane Proteins / physiology*
-
Mice
-
Mice, Inbred C57BL
-
Mice, Transgenic
-
Ovalbumin / immunology
Substances
-
Antibodies, Blocking
-
Antibodies, Monoclonal
-
Antigens, CD
-
CD27 Ligand
-
CD40 Antigens
-
Cd70 protein, mouse
-
Epitopes, T-Lymphocyte
-
Growth Inhibitors
-
Membrane Proteins
-
Ovalbumin