B7-1 and B7-2 costimulatory molecules activate differentially the Th1/Th2 developmental pathways: application to autoimmune disease therapy

Cell. 1995 Mar 10;80(5):707-18. doi: 10.1016/0092-8674(95)90349-6.

Abstract

CD4 T helper precursor cells mature along two alternative pathways, Th1 and Th2. Here we show that these pathways are differentially activated by two costimulatory molecules, B7-1 and B7-2. Using anti-B7 antibodies, this developmental step was manipulated both in vitro and in vivo in experimental allergic encephalomyelitis (EAE). Anti-B7-1 reduced the incidence of disease while anti-B7-2 increased disease severity. Neither antibody affected overall T cell induction but rather altered cytokine profile. Administration of anti-B7-1 at immunization resulted in predominant generation of Th2 clones whose transfer both prevented induction of EAE and abrogated established disease. Since co-treatment with anti-IL-4 antibody prevented disease amelioration, costimulatory molecules may directly affect initial cytokine secretion. Thus, interaction of B7-1 and B7-2 with shared counterreceptors CD28 and CTLA-4 results in very different outcomes in clinical disease by influencing commitment of precursors to a Th1 or Th2 lineage.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / therapeutic use
  • Antigens, CD*
  • B7-1 Antigen / immunology*
  • B7-2 Antigen
  • Cell Differentiation
  • Cells, Cultured
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Encephalomyelitis, Autoimmune, Experimental / prevention & control
  • Female
  • Immunotherapy, Adoptive
  • Interferon-gamma / biosynthesis
  • Interleukin-4 / biosynthesis
  • Interleukin-4 / physiology
  • Lymph Nodes / cytology
  • Lymph Nodes / metabolism
  • Membrane Glycoproteins / immunology*
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Myelin Basic Protein / immunology
  • Proteolipids / administration & dosage
  • Th1 Cells / cytology
  • Th1 Cells / immunology*
  • Th2 Cells / cytology
  • Th2 Cells / immunology*
  • Vaccination

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • B7-1 Antigen
  • B7-2 Antigen
  • Cd86 protein, mouse
  • Membrane Glycoproteins
  • Myelin Basic Protein
  • Proteolipids
  • Interleukin-4
  • Interferon-gamma