| 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. |