CTLA-4 can function as a negative regulator of T cell activation

Immunity. 1994 Aug;1(5):405-13. doi: 10.1016/1074-7613(94)90071-x.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Abatacept
  • Animals
  • Antibodies / pharmacology
  • Antibodies, Monoclonal / pharmacology
  • Antigens, CD
  • Antigens, Differentiation / chemistry
  • Antigens, Differentiation / immunology
  • Antigens, Differentiation / physiology*
  • Base Sequence
  • CD28 Antigens / pharmacology
  • CD3 Complex / immunology
  • 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*

Substances

  • Antibodies
  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Differentiation
  • CD28 Antigens
  • CD3 Complex
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Ctla4 protein, mouse
  • Immunoconjugates
  • Immunoglobulin Fab Fragments
  • Immunoglobulin Fragments
  • Membrane Proteins
  • Receptors, Antigen, T-Cell
  • Abatacept