P-selectin directs T lymphocyte-mediated injury in delayed-type hypersensitivity responses: studies in glomerulonephritis and cutaneous delayed-type hypersensitivity

Eur J Immunol. 1996 Feb;26(2):454-60. doi: 10.1002/eji.1830260228.


The role of P-selectin in T-lymphocyte accumulation and injury was studied in delayed-type hypersensitivity (DTH) responses in the skin and glomeruli of rats. Sprague Dawley rats were sensitized to sheep globulin and challenged 5 days later in the skin by subcutaneous injection and simultaneously in glomeruli by intravenous injection of a subnephritogenic dose of sheep anti-rat glomerular basement membrane globulin. This resulted in cutaneous and glomerular T lymphocyte-dependent macrophage influx and injury characteristic of DTH. Up-regulation of P-selectin expression on endothelial cells was observed in both inflammatory lesions. Treatment of rats with anti-CD5 antibody immediately prior to antigen challenge prevented the development of injury as assessed by measurement of proteinuria and skin swelling, as well as local T cell and macrophage accumulation in the glomerulus and in the skin, but did not block up-regulation endothelial cell P-selectin. Treatment with anti-CD4 antibody produced similar results. Blocking P-selectin in vivo with a functionally inhibitory antibody prevented development of proteinuria and skin swelling following antigen challenge. Local accumulation of T cells and macrophages was markedly attenuated in glomeruli and the skin and up-regulation of endothelial cell P-selectin was prevented. These data demonstrate that P-selectin is locally up-regulated on endothelial cells in T cell-dependent glomerular and cutaneous inflammation and suggests a pivotal functional role for P-selectin in local T cell recruitment and subsequent injury in DTH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Basement Membrane / immunology
  • CD4 Antigens / immunology
  • CD5 Antigens / immunology
  • Cytotoxicity, Immunologic / drug effects*
  • Disease Models, Animal
  • Glomerulonephritis / etiology
  • Glomerulonephritis / immunology*
  • Glomerulonephritis / pathology
  • Hypersensitivity, Delayed / etiology
  • Hypersensitivity, Delayed / immunology*
  • Kidney Glomerulus / immunology
  • Kidney Glomerulus / pathology
  • Lymphocyte Count
  • Male
  • P-Selectin / immunology
  • P-Selectin / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Skin / immunology*
  • Skin / pathology
  • T-Lymphocytes, Cytotoxic / drug effects*


  • Antibodies, Monoclonal
  • CD4 Antigens
  • CD5 Antigens
  • P-Selectin