Association of B7-1 co-stimulation with the development of graft arterial disease. Studies using mice lacking B7-1, B7-2, or B7-1/B7-2

Am J Pathol. 2000 Aug;157(2):473-84. doi: 10.1016/S0002-9440(10)64559-2.

Abstract

To investigate the roles of B7-1 and/or B7-2 co-stimulatory molecule in the development of graft arterial disease (GAD), major histocompatibility complex (MHC) class II-mismatched allograft hearts were transplanted into wild-type, B7-1(-/-), B7-2(-/-), or B7-1/B7-2(-/-) recipient mice. Grafts were explanted at 4 or 8 weeks and used for histological and immunohistochemical analyses, RNase protection assay, and flow cytometry of graft infiltrating cells. Grafts in wild-type recipients showed macrophage, recipient MHC class II, and B7 molecule co-localization by immunohistochemistry to GAD lesions. Flow cytometry revealed that CD11b(+) and MHC class II(+) graft infiltrating cells expressed B7-1 more than B7-2, whereas B7-2 expression was predominant in CD11b(-) cells at 4 and 8 weeks. GAD was significantly attenuated in the allografts in B7-1(-/-) and B7-1/B7-2(-/-) but not in B7-2(-/-) recipients compared to wild-type hosts. Interferon-gamma mRNA levels were comparable in all graft combinations, whereas interleukin-4 mRNA levels decreased in grafts in B7-2 deficient hosts, but did not correlate with GAD attenuation. The findings indicate distinct roles for B7-1 and B7-2 co-stimulatory molecules in the development of GAD, potentially because of differential expression of B7-1 and B7-2 molecules on distinct stimulator and/or effector cell populations.

Publication types

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

MeSH terms

  • Animals
  • Antigen-Presenting Cells / physiology
  • Antigens, CD / analysis
  • Antigens, CD / genetics
  • Antigens, CD / physiology
  • B-Lymphocytes / chemistry
  • B-Lymphocytes / cytology
  • B7-1 Antigen / analysis
  • B7-1 Antigen / genetics
  • B7-1 Antigen / physiology*
  • B7-2 Antigen
  • CD4-Positive T-Lymphocytes / chemistry
  • CD4-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / chemistry
  • CD8-Positive T-Lymphocytes / cytology
  • Chemokines / genetics
  • Cytokines / genetics
  • Female
  • Flow Cytometry
  • Gene Expression Regulation
  • Genotype
  • Graft Occlusion, Vascular / etiology*
  • Graft Rejection / complications
  • Graft Rejection / physiopathology
  • Heart Transplantation
  • Histocompatibility Antigens Class II / analysis
  • Immunohistochemistry
  • Macrophages / chemistry
  • Macrophages / cytology
  • Male
  • Membrane Glycoproteins / analysis
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology
  • Mice
  • Mice, Inbred C57BL
  • Time Factors
  • Transplantation, Homologous

Substances

  • Antigens, CD
  • B7-1 Antigen
  • B7-2 Antigen
  • Cd86 protein, mouse
  • Chemokines
  • Cytokines
  • Histocompatibility Antigens Class II
  • Membrane Glycoproteins