PMID:7882171

Citation	Walunas, TL, Lenschow, DJ, Bakker, CY, Linsley, PS, Freeman, GJ, Green, JM, Thompson, CB and Bluestone, JA (1994) CTLA-4 can function as a negative regulator of T cell activation. Immunity 1:405-13
Abstract	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.
Links	PubMed
Keywords	Animals; Antibodies/pharmacology; Antibodies, Monoclonal/pharmacology; Antigens, CD; Antigens, CD28/pharmacology; Antigens, CD3/immunology; Antigens, Differentiation/chemistry; Antigens, Differentiation/immunology; Antigens, Differentiation/physiology; Base Sequence; CTLA-4 Antigen; Cell Division/immunology; Humans; Immunoconjugates; Immunoglobulin Fab Fragments; Immunoglobulin Fragments/immunology; Immunoglobulin Fragments/pharmacology; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Male; Membrane Proteins/chemistry; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred DBA; Molecular Sequence Data; Receptors, Antigen, T-Cell/physiology; T-Lymphocytes/cytology; T-Lymphocytes/immunology
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