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Publication : The lack of CD8 alpha cytoplasmic domain resulted in a dramatic decrease in efficiency in thymic maturation but only a moderate reduction in cytotoxic function of CD8+ T lymphocytes.

First Author  Fung-Leung WP Year  1993
Journal  Eur J Immunol Volume  23
Issue  11 Pages  2834-40
PubMed ID  8223860 Mgi Jnum  J:113044
Mgi Id  MGI:3664377 Doi  10.1002/eji.1830231117
Citation  Fung-Leung WP, et al. (1993) The lack of CD8 alpha cytoplasmic domain resulted in a dramatic decrease in efficiency in thymic maturation but only a moderate reduction in cytotoxic function of CD8+ T lymphocytes. Eur J Immunol 23(11):2834-40
abstractText  The glycoprotein CD8 is believed to play an important role in the maturation and function of MHC class I-restricted T lymphocytes. CD8 has been proposed to function as a co-receptor of the TcR to participate in signal transduction, possibly through its cytoplasmic domain that binds to protein tyrosine kinase p56lck. A T cell-specific transgene encoding CD8 alpha truncated at the cytoplasmic domain ('tailless CD8 alpha'), was introduced into CD8 alpha-deficient mice. This animal model was used to study the role of the CD8 cytoplasmic domain in T cell ontogeny and function. 'Tailless CD8 alpha' was expressed on the cell surface of thymocytes and peripheral T cells. A small population of peripheral CD4- T cells (6% of T lymphocytes) was found to have cell surface expression of 'tailless CD8 alpha' and endogenous CD8 beta, indicating that these cells may belong to the CD8+ T cell lineage. A consistent result was obtained from CD8 alpha-deficient mice bearing the 'tailless CD8 alpha' and the MHC class I-restricted 2C TcR transgenes. A small population of CD4- T cells expressing CD8 beta, the 'tailless CD8 alpha' and the 2C TcR transgenes was present in the periphery of these mice in a selecting background, but was absent in a deleting background. When 'tailless CD8 alpha' mice were infected with lymphocytic choriomeningitis virus (LCMV), the peripheral CD8+ CD4- T cell subset expanded dramatically and a significant LCMV-specific cytolytic activity was detected. The results suggest that the cytoplasmic portion of CD8 alpha is not absolutely required but dramatically enhances the efficiency of thymic maturation of CD8+ T cells. The lack of CD8 alpha cytoplasmic domain in peripheral CD8+ T cells does not abolish the generation of cytotoxicity in response to an in vivo LCMV infection, although the cytolytic activity is slightly reduced compared to that in control mice.
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