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

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 p56(lck). 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.