Decreased dependence of myelin basic protein-reactive T cells on CD28-mediated costimulation in multiple sclerosis patients. A marker of activated/memory T cells

J Clin Invest. 1998 Feb 15;101(4):725-30. doi: 10.1172/JCI1528.


Although multiple sclerosis (MS) patients and healthy individuals have similar frequencies of myelin basic protein (MBP)-specific T cells, the activation state of these cells has not been well characterized. Therefore, we investigated the dependence of MBP-reactive T cells on CD28-mediated costimulation in MS patients, healthy controls, and stroke patients. MBP-reactive T cells from healthy controls and stroke patients failed to proliferate efficiently when costimulation was blocked using anti-CD28, consistent with a naive T cell response. In contrast, MBP-specific T cell proliferation was not inhibited, or was only partially inhibited when CD28-mediated costimulation was blocked in MS patients. Blockade of CD28 failed to inhibit tetanus toxoid-specific T cell proliferation in both the controls and MS patients, demonstrating that memory cells are not dependent on CD28-mediated costimulation. Limiting dilution analysis indicated that the frequency of MBP-reactive T cells was significantly decreased in healthy controls compared with MS patients when CD28-mediated costimulation was blocked. These data suggest that MBP-reactive T cells are more likely to have been activated in vivo and/or differentiated into memory T cells in MS patients compared with controls, indicating that these cells may be participating in the pathogenesis of MS.

Publication types

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

MeSH terms

  • Abatacept
  • Adult
  • Antigens, CD / immunology
  • Antigens, Differentiation / immunology
  • B7-2 Antigen
  • CD28 Antigens / immunology*
  • CTLA-4 Antigen
  • Cell Division
  • Humans
  • Immunoconjugates*
  • Immunoglobulins / immunology
  • Lymphocyte Count
  • Membrane Glycoproteins / immunology
  • Middle Aged
  • Multiple Sclerosis / blood
  • Multiple Sclerosis / immunology*
  • Myelin Basic Protein / immunology*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*


  • Antigens, CD
  • Antigens, Differentiation
  • B7-2 Antigen
  • CD28 Antigens
  • CD86 protein, human
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Immunoconjugates
  • Immunoglobulins
  • Membrane Glycoproteins
  • Myelin Basic Protein
  • Abatacept