CTLA4 mediates antigen-specific apoptosis of human T cells.
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.
Gribben
J G
JG
Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA 02115.
Freeman
G J
GJ
Boussiotis
V A
VA
Rennert
P
P
Jellis
C L
CL
Greenfield
E
E
Barber
M
M
Restivo
V A
VA
Ke
X
X
Gray
G S
GS
D000069594:Abatacept; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000032:analysis / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology; D017209:Apoptosis / Q000276:immunology*; D018106:CD28 Antigens / Q000032:analysis; D060908:CTLA-4 Antigen; D002455:Cell Division; D002478:Cells, Cultured; D003429:Cross Reactions; D018604:Epitope Mapping; D015809:HLA-DR7 Antigen / Q000276:immunology; D006801:Humans; D018796:Immunoconjugates; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000954:Antigens, Surface; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D015809:HLA-DR7 Antigen; D018796:Immunoconjugates; D007376:Interleukin-2; D010835:Phytohemagglutinins; D000069594:Abatacept