ICOS/B7RP-1 interference in mouse kidney transplantation

Transplantation. 2007 Jul 27;84(2):223-30. doi: 10.1097/01.tp.0000267439.15439.61.


Background: Activated T cells play a key role in allograft rejection. T cell activation requires signaling via the T cell receptor as well as costimulatory signals. Inducible costimulatory molecule (ICOS), with its ligand B7RP-1, is a recently discovered costimulatory molecule of the CD28 family. The role of this signaling pathway during the early phases of kidney allograft rejection is not clear so far.

Methods: Kidneys were orthotopically transplanted from BALB/c to C57BL/6 mice. Animals were assigned to five experimental groups: blocking anti-ICOS monoclonal antibody, ICOS fusion protein, anti-B7RP1 monoclonal antibody, B7RP-1 fusion protein, and control immunoglobulin G.

Results: Survival was significantly reduced in animals treated with ICOS monoclonal antibody (mAb) and B7RP-1 Fc as compared with controls. These animals had also a lower number of apoptotic graft infiltrating T cells, whereas the expression of intracellular interferon-gamma in CD3CD4 T cells was increased. Animals treated with ICOS Fc and B7RP-1 mAb had similar survival and numbers of apoptotic T cells as compared with controls.

Conclusions: In summary, the blockade of ICOS with ICOS mAb or B7RP-1 Fc reduced the amount of apoptosis of infiltrating lymphocytes and resulted in continuous inflammatory processes with progressive tissue damage and graft failure.

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Antigens, Differentiation, T-Lymphocyte / immunology
  • Antigens, Differentiation, T-Lymphocyte / therapeutic use*
  • Apoptosis
  • B7-1 Antigen / immunology
  • B7-1 Antigen / therapeutic use*
  • CD3 Complex / biosynthesis
  • CD3 Complex / genetics
  • CD4 Immunoadhesins / biosynthesis
  • CD4 Immunoadhesins / genetics
  • Disease Models, Animal
  • Flow Cytometry
  • Gene Expression
  • Graft Rejection / drug therapy*
  • Graft Rejection / immunology
  • Graft Rejection / metabolism
  • Graft Survival
  • In Situ Nick-End Labeling
  • Inducible T-Cell Co-Stimulator Ligand
  • Inducible T-Cell Co-Stimulator Protein
  • Intracellular Fluid / metabolism
  • Kidney Transplantation / immunology*
  • Kidney Transplantation / pathology
  • Ligands
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • RNA, Messenger / genetics
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology


  • Antibodies, Monoclonal
  • Antigens, Differentiation, T-Lymphocyte
  • B7-1 Antigen
  • CD3 Complex
  • CD3 antigen, gamma chain
  • CD4 Immunoadhesins
  • Icos protein, mouse
  • Inducible T-Cell Co-Stimulator Ligand
  • Inducible T-Cell Co-Stimulator Protein
  • Ligands
  • RNA, Messenger