Preferential contribution of B7-H1 to programmed death-1-mediated regulation of hapten-specific allergic inflammatory responses

Eur J Immunol. 2003 Oct;33(10):2773-82. doi: 10.1002/eji.200324084.


Programmed death-1 (PD-1) and its ligands, B7-H1/PD-L1 and B7-DC/PD-L2, are new CD28-B7 family members that may be involved in the regulation of immune responses. We examined the roles of these molecules in mouse hapten-induced contact hypersensitivity (CH). Administration of anti-PD-1 mAb at sensitization significantly enhanced and prolonged ear swelling. Treatment with anti-B7-H1 mAb, but not anti-B7-DC mAb, also enhanced CH reactions. The anti-PD-1 mAb treatment at sensitization significantly increased the T cell number of draining lymph nodes (DLN). B7-H1 was induced on activated T cells and antigen-presenting cells (APC) in the skin and the DLN, whereas B7-DC expression was restricted to dendritic cells (DC) in the dermis and the DLN. A particular subset of DC, B7-H1(+)B7-DC(-)CD86(low), was found in sensitized DLN. The blockade of B7-H1, but not B7-DC, dramatically enhanced the initial T cell proliferative responses against hapten-pulsed DLN APC, suggesting the preferential contribution of B7-H1 to the T cell-APC interaction. Our results demonstrate the regulatory role of PD-1 and the differential roles of B7-H1 and B7-DC in hapten-induced immune responses. The PD-1-B7-H1 pathway may play a unique role in regulating inflammatory responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antigen-Presenting Cells / chemistry
  • Antigen-Presenting Cells / physiology
  • Antigens, CD
  • Antigens, Differentiation / physiology
  • Antigens, Surface*
  • Apoptosis Regulatory Proteins
  • B7-1 Antigen / analysis
  • B7-1 Antigen / physiology*
  • B7-H1 Antigen
  • Blood Proteins*
  • CTLA-4 Antigen
  • Dermatitis, Contact / etiology*
  • Female
  • Haptens / immunology
  • Membrane Glycoproteins
  • Mice
  • Mice, Inbred BALB C
  • Peptides*
  • Programmed Cell Death 1 Ligand 2 Protein
  • Programmed Cell Death 1 Receptor
  • Proteins / physiology*


  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Differentiation
  • Antigens, Surface
  • Apoptosis Regulatory Proteins
  • B7-1 Antigen
  • B7-H1 Antigen
  • Blood Proteins
  • CTLA-4 Antigen
  • Cd274 protein, mouse
  • Ctla4 protein, mouse
  • Haptens
  • Membrane Glycoproteins
  • Pdcd1 protein, mouse
  • Pdcd1lg2 protein, mouse
  • Peptides
  • Programmed Cell Death 1 Ligand 2 Protein
  • Programmed Cell Death 1 Receptor
  • Proteins