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CD48-deficient mice have a pronounced defect in CD4(+) T cell activation
J González-Cabrero1, C J Wise, Y Latchman
1Unidad de Investigación, Instituto de Investigaciones Médicas, Fundación Jiménez Díaz, Madrid 28040 Spain.
Abstract:
We have generated mice deficient in the expression of the lymphocyte cell surface antigen CD48 (Blast-1, BCM1, sgp-60) by gene targeting in embryonic stem cells. Mice homozygous for the CD48 mutation (CD48(-/-) mice) are severely impaired in CD4(+) T cell activation. Proliferative responses to mitogens, anti-CD3 mAb, and alloantigen are all reduced. Experiments in which T cells and antigen-presenting cells from either wild-type or CD48(-/-) mice were cocultured reveal that CD48 is important on both T cells and antigen-presenting cells. The most dramatic impairment was observed in experiments in which highly purified T cells were stimulated through the T cell receptor in the presence of the phorbol ester, phorbol 12-myristate 13-acetate. The results of these experiments raise the possibility that CD48 plays a role in signaling through the T cell receptor.
Insights
Mice lacking the CD48 antigen show significantly reduced CD4(+) T cell activation, impacting immune responses. This suggests CD48 is crucial for T cell receptor signaling in both T cells and antigen-presenting cells.
Area of Science:
- Immunology
- Molecular Biology
Background:
- CD48 is a lymphocyte cell surface antigen.
- Its precise role in T cell activation is not fully understood.
Purpose of the Study:
- To investigate the function of CD48 in T cell activation and immune responses.
- To determine the cell-specific requirements for CD48 in T cell signaling.
Main Methods:
- Gene targeting in embryonic stem cells to create CD48-deficient mice (CD48(-/-)).
- Assessing T cell activation through proliferation assays using mitogens, anti-CD3 mAb, and alloantigen.
- Coculture experiments with purified T cells and antigen-presenting cells from wild-type and CD48(-/-) mice.
Main Results:
- CD48(-/-) mice exhibited severely impaired CD4(+) T cell activation.
- Reduced proliferative responses were observed in response to various stimuli.
- CD48 was found to be important on both T cells and antigen-presenting cells.
- Significant impairment in T cell receptor signaling was noted when CD48 was absent.
Conclusions:
- CD48 plays a critical role in CD4(+) T cell activation.
- The antigen is essential for T cell responses mediated by both T cells and antigen-presenting cells.
- These findings suggest CD48 is involved in T cell receptor signaling pathways.
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