Functional activation of lymphocyte CD44 in peripheral blood is a marker of autoimmune disease activity

Pila Estess, Heather C. DeGrendele, Virginia Pascual, Mark H. Siegelman

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

Interactions between complementary receptors on leukocytes and endothelial cells play a central role in regulating extravasation from the blood and thereby affect both normal-and pathologic inflammatory responses. CD44 on lymphocytes that has been 'activated' to bind its principal ligand hyaluronate (HA) on endothelium can mediate the primary adhesion (rolling) of lymphocytes to vascular endothelial cells under conditions of physiologic shear stress, and this interaction is used for activated T cell extravasation into an inflamed site in vivo in mice (DeGrendele, H.C., P. Estess, L.J. Picker, and M.H. Siegelman. 1996. J. Exp. Med. 183:1119-1130. DeGrendele, H.D., P. Estess, and M.H. Siegelman. 1997. Science. 278:672-675. DeGrendele, H.C., P. Estess, and M.H. Siegelman. 1997. J. Immunol. 159: 2549-2553). Here, we have investigated the role of lymphocyte-borne-activated CD44 in the human and show that CD44-dependent primary adhesion is induced in human peripheral blood T cells through T cell receptor triggering. In addition, lymphocytes capable of CD44/HA-dependent rolling interactions can be found resident within inflamed tonsils. In analysis of peripheral bloods of patients from a pediatric rheumatology clinic, examining systemic lupus erythematosus, and a group of chronic arthropathies, expression of CD44-dependent primary adhesion strongly correlates with concurrent symptomatic disease, with 85% of samples from clinically active patients showing elevated levels of rolling activity (compared with only 4% of inactive patients). These rolling interactions are predominantly mediated by T cells. The results suggest that circulating T lymphocytes bearing activated CD44 are elevated under conditions of chronic inflammation and that these may represent a pathogenically important subpopulation of activated circulating cells that may provide a reliable marker for autoimmune or chronic inflammatory disease activity.

Original languageEnglish (US)
Pages (from-to)1173-1182
Number of pages10
JournalJournal of Clinical Investigation
Volume102
Issue number6
DOIs
StatePublished - Sep 15 1998

Keywords

  • Adhesion
  • Arthritis
  • Hyaluronate
  • Inflammation
  • SLE

ASJC Scopus subject areas

  • Medicine(all)

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