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Thy-1 Signaling in the Context of Costimulation Provided by Dendritic Cells Provides Signal 1 for T Cell Proliferation and Cytotoxic Effector Molecule Expression, but Fails to Trigger Delivery of the Lethal Hit
- Source :
- The Journal of Immunology. 171:69-77
- Publication Year :
- 2003
- Publisher :
- The American Association of Immunologists, 2003.
-
Abstract
- Cross-linking of the GPI-anchored protein Thy-1 results in T cell proliferation and IL-2 synthesis. However, the exact function of Thy-1 in the process of T cell activation remains unknown, as does the effect of costimulation on Thy-1-driven T cell responses. In this study, we have investigated the ability of Thy-1 to substitute for traditional signal 1 in the context of costimulation provided by dendritic cells. Dendritic cells dramatically enhanced T cell proliferation and IL-2 synthesis in response to Thy-1 triggering by anti-Thy-1 mAb. This effect was not dependent on dendritic cell Fcγ receptors, but was a result of B7-mediated costimulation (signal 2). T cells were also activated when microbeads coated with a combination of anti-Thy-1 and anti-CD28 mAbs were used to supply signals 1 and 2, respectively. Thy-1-stimulated T cells adhere to target cells and express perforin, granzyme B, and Fas ligand, but fail to kill target cells due to an inability to reorganize their secretion machinery. Moreover, in contrast to TCR signaling, Thy-1 triggering failed to induce cytotoxicity in redirected lysis assays. We conclude that Thy-1 triggering can partially substitute for signal 1, which, in combination with a strong signal 2, leads to robust T cell proliferation, IL-2 synthesis, and cytotoxic effector molecule expression, but does not induce cytolytic function. The block at the level of cytotoxic effector function that results when T cells are activated in the absence of a classical, Ag-specific signal 1 may constitute a mechanism to ensure the specificity of CTL responses and prevent potentially harmful promiscuous cytotoxicity.
- Subjects :
- Cytotoxicity, Immunologic
T cell
Molecular Sequence Data
Immunology
Mice, Transgenic
Streptamer
Biology
Lymphocyte Activation
Mice
Interleukin 21
CD28 Antigens
Tumor Cells, Cultured
medicine
Animals
Immunology and Allergy
Cytotoxic T cell
Amino Acid Sequence
Antigen-presenting cell
Mice, Knockout
Mice, Inbred BALB C
Receptors, IgG
Antibodies, Monoclonal
Dendritic Cells
Dendritic cell
Cytotoxicity Tests, Immunologic
Natural killer T cell
Up-Regulation
Cell biology
Granzyme B
medicine.anatomical_structure
Receptor-CD3 Complex, Antigen, T-Cell
Interleukin-2
Thy-1 Antigens
Signal Transduction
T-Lymphocytes, Cytotoxic
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 171
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....6cb27a89378fee0c360dda1decbd39a1