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The lack of CD8 alpha cytoplasmic domain resulted in a dramatic decrease in efficiency in thymic maturation but only
W P Fung-Leung1, M C Louie, A Limmer
1Ontario Cancer Institute, Department of Medical Biophysics and Immunology, University of Toronto, Canada.
European Journal of Immunology
|November 1, 1993
Summary
The CD8 cytoplasmic domain enhances T cell maturation but is not essential for cytotoxic T cell function. CD8-deficient mice with truncated CD8 alpha showed reduced, yet present, T cell cytotoxicity against viral infections.
Area of Science:
- Immunology
- Molecular Biology
- T cell biology
Background:
- The glycoprotein CD8 is crucial for MHC class I-restricted T lymphocyte maturation and function.
- CD8 is proposed to act as a T cell receptor (TcR) co-receptor, aiding signal transduction via its cytoplasmic domain binding to p56lck.
- The precise role of the CD8 cytoplasmic domain in T cell development and function requires further investigation.
Purpose of the Study:
- To investigate the role of the CD8 cytoplasmic domain in T cell ontogeny and function using a novel mouse model.
- To determine if the CD8 cytoplasmic domain is essential for the development and cytotoxic activity of CD8+ T cells.
Main Methods:
- Generation of CD8 alpha-deficient mice expressing a truncated "tailless CD8 alpha" transgene.
- Analysis of thymocyte and peripheral T cell populations using flow cytometry.
- Assessment of T cell maturation and function in response to lymphocytic choriomeningitis virus (LCMV) infection.
Main Results:
- "Tailless CD8 alpha" was expressed on thymocytes and peripheral T cells, with a subset of CD4- T cells expressing both "tailless CD8 alpha" and CD8 beta.
- In mice with "tailless CD8 alpha" and 2C TcR transgenes, CD4- T cells were observed in a selecting but not deleting background.
- Infection with LCMV led to dramatic expansion of the peripheral CD8+ CD4- T cell subset and significant LCMV-specific cytolytic activity.
Conclusions:
- The CD8 alpha cytoplasmic domain significantly enhances thymic maturation efficiency of CD8+ T cells but is not absolutely required.
- Peripheral CD8+ T cells lacking the CD8 alpha cytoplasmic domain can still generate cytotoxicity against viral infections, albeit with slightly reduced activity.