CTLA-4 can function as a negative regulator of T cell activation.
CD28 and CTLA-4 are related glycoproteins found on T cells. Ligation of CD28 following antigen receptor engagement provides a costimulatory signal required for T cell activation. Anti-CTLA-4 antibodies were generated to examine the role of the CTLA-4 receptor on murine T cells. Expression of CTLA-4 as a homodimer is up-regulated 2-3 days following T cell activation. Anti-CTLA-4 antibodies and Fab fragments augmented T cell proliferation in an allogeneic MLR. However, when optimal costimulation and Fc cross-linking were present, anti-CTLA-4 Mabs inhibited T cell proliferation. Together, these results suggest that the MAb may obstruct the interaction of CTLA-4 with its natural ligand and block a negative signal, or directly signal T cells to down-regulate immune function.
Walunas
T L
TL
University of Chicago, Illinois 60637.
Lenschow
D J
DJ
Bakker
C Y
CY
Linsley
P S
PS
Freeman
G J
GJ
Green
J M
JM
Thompson
C B
CB
Bluestone
J A
JA
D000069594:Abatacept; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D001483:Base Sequence; D018106:CD28 Antigens / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D060908:CTLA-4 Antigen; D002455:Cell Division / Q000276:immunology; D006801:Humans; D018796:Immunoconjugates; D007140:Immunoglobulin Fab Fragments; D007128:Immunoglobulin Fragments / Q000276:immunology / Q000494:pharmacology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D000906:Antibodies; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018106:CD28 Antigens; D017252:CD3 Complex; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D007140:Immunoglobulin Fab Fragments; D007128:Immunoglobulin Fragments; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; D000069594:Abatacept