CTLA-4 blockade enhances clinical disease and cytokine production during experimental allergic encephalomyelitis

J Immunol. 1996 Aug 15;157(4):1333-6.


The B7 family of cell surface molecules expressed on APC provides accessory signals to T cells via either CD28 or CTLA-4. However, while CD28 transduces a costimulatory signal that is required for an optimal immune response, CTLA-4 transmits a negative signal. These studies use an anti-CTLA-4 mAb to directly address the role of this T cell surface molecule in experimental allergic encephalomyelitis (EAE). CTLA-4 regulation of disease was assessed during initial immune cell interactions and during the effector stage of the encephalitogenic immune response. The effects of anti-CTLA-4 treatment were schedule dependent. CTLA-4 blockade during the onset of clinical symptoms markedly exacerbated disease, enhancing mortality. Disease exacerbation was associated with enhanced production of the encephalitogenic cytokines TNF-alpha, IFN-gamma and IL-2. Hence, CTLA-4 regulates the intensity of the autoimmune response in EAE, attenuating inflammatory cytokine production and clinical disease manifestations.

Publication types

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

MeSH terms

  • Abatacept
  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antigens, CD / physiology
  • Antigens, Differentiation / physiology*
  • Autoimmune Diseases / immunology*
  • B7-1 Antigen / physiology
  • B7-2 Antigen
  • CD28 Antigens / physiology*
  • CTLA-4 Antigen
  • Cytokines / biosynthesis*
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Female
  • Humans
  • Immunoconjugates*
  • Interferon-gamma / biosynthesis
  • Interleukin-2 / biosynthesis
  • Membrane Glycoproteins / physiology
  • Mice
  • Rats
  • Signal Transduction / drug effects
  • T-Lymphocytes, Cytotoxic / immunology*
  • Tumor Necrosis Factor-alpha / biosynthesis


  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Differentiation
  • B7-1 Antigen
  • B7-2 Antigen
  • CD28 Antigens
  • CD86 protein, human
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Cd86 protein, mouse
  • Cd86 protein, rat
  • Ctla4 protein, mouse
  • Ctla4 protein, rat
  • Cytokines
  • Immunoconjugates
  • Interleukin-2
  • Membrane Glycoproteins
  • Tumor Necrosis Factor-alpha
  • Abatacept
  • Interferon-gamma