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 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.
Fung-Leung
W P
WP
Ontario Cancer Institute, Department of Medical Biophysics and Immunology, University of Toronto, Canada.
Louie
M C
MC
Limmer
A
A
Ohashi
P S
PS
Ngo
K
K
Chen
L
L
Kawai
K
K
Lacy
E
E
Loh
D Y
DY
Mak
T W
TW
D000818:Animals; D001483:Base Sequence; D016827:CD8 Antigens / Q000235:genetics*; D002454:Cell Differentiation; D003593:Cytoplasm / Q000276:immunology; D004247:DNA / Q000235:genetics; D008216:Lymphocytic Choriomeningitis / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D017384:Sequence Deletion; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology*
D016827:CD8 Antigens; D004247:DNA