Proc Natl Acad Sci U S A 92(3): 811-815
CTLA4 mediates antigen-specific apoptosis of human T cells.
G Freeman
V Boussiotis
P Rennert
C Jellis
E Greenfield
M Barber
V Restivo
X Ke
G Gray
Abstract
The regulation of T cell-mediated immune responses requires a balance between amplification and generation of effector function and subsequent selective termination by clonal deletion. Although apoptosis of previously activated T cells can be induced by signaling of the tumor necrosis factor receptor family, these molecules do not appear to regulate T-cell clonal deletion in an antigen-specific fashion. We demonstrate that cross-linking of the inducible T-cell surface molecule CTLA4 can mediate apoptosis of previously activated human T lymphocytes. This function appears to be antigen-restricted, since a concomitant signal T-cell receptor signal is required. Regulation of this pathway may provide a novel therapeutic strategy to delete antigen-specific activated T cells.
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