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Direct demonstration of the CD27 molecule involved in the negative regulatory effect on T cell activation
K Sugita1, T Tanaka, J M Doshen
1Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Abstract:
CD27 is a member of the nerve growth factor/tumor necrosis factor receptor family and appears to play an important role in the process of T cell activation. We have previously shown that perturbation of the CD27 molecule by anti-1A4 (CD27) mAb inhibits T cell proliferation induced by various stimuli. To further determine the molecular basis of this inhibition of T cell proliferation by anti-1A4 mAb, we have established CD27-transfectant lines. Introduction of the human CD27 cDNA to ovalbumin-specific I-Ad-restricted murine T cell hybridomas significantly reduced their antigen-specific IL-2 production. In addition, treatment of these human CD27 transfectants with an anti-CD27 mAb (anti-1A4) further reduced their IL-2 production. These results provide direct evidence that CD27 plays a crucial role in the process of T cell activation.
Insights
CD27, a key T cell activator, was studied for its role in immune responses. Introducing CD27 into T cells reduced IL-2 production, confirming its crucial function in T cell activation.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- CD27 is a receptor in the tumor necrosis factor superfamily.
- CD27 signaling is implicated in T cell activation and immune responses.
- Previous studies showed anti-CD27 antibodies inhibit T cell proliferation.
Purpose of the Study:
- To elucidate the molecular mechanisms by which CD27 influences T cell activation.
- To investigate the impact of CD27 expression on T cell cytokine production.
Main Methods:
- Established CD27-transfectant murine T cell hybridoma lines.
- Introduced human CD27 cDNA into T cell hybridomas.
- Assessed antigen-specific IL-2 production.
- Treated transfectants with anti-CD27 mAb (anti-1A4).
Main Results:
- Transfection of CD27 significantly reduced antigen-specific IL-2 production in T cell hybridomas.
- Treatment with anti-CD27 mAb further diminished IL-2 production in CD27-expressing cells.
- Demonstrated a direct correlation between CD27 expression and reduced IL-2 secretion.
Conclusions:
- CD27 plays a critical role in regulating T cell activation.
- CD27 signaling negatively impacts IL-2 production, suggesting a modulatory function in T cell responses.