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

89 Citations (Scopus)

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
StatePublished - Sep 15 1998

Fingerprint

Lymphocyte Activation
Autoimmune Diseases
Lymphocytes
T-Lymphocytes
Endothelial Cells
Joint Diseases
Palatine Tonsil
Rheumatology
T-Cell Antigen Receptor
Systemic Lupus Erythematosus
Endothelium
Blood Cells
Leukocytes
Chronic Disease
Pediatrics
Ligands
Inflammation

Keywords

  • Adhesion
  • Arthritis
  • Hyaluronate
  • Inflammation
  • SLE

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Estess, P., DeGrendele, H. C., Pascual, V., & Siegelman, M. H. (1998). Functional activation of lymphocyte CD44 in peripheral blood is a marker of autoimmune disease activity. Journal of Clinical Investigation, 102(6), 1173-1182.

Functional activation of lymphocyte CD44 in peripheral blood is a marker of autoimmune disease activity. / Estess, Pila; DeGrendele, Heather C.; Pascual, Virginia; Siegelman, Mark H.

In: Journal of Clinical Investigation, Vol. 102, No. 6, 15.09.1998, p. 1173-1182.

Research output: Contribution to journalArticle

Estess, P, DeGrendele, HC, Pascual, V & Siegelman, MH 1998, 'Functional activation of lymphocyte CD44 in peripheral blood is a marker of autoimmune disease activity', Journal of Clinical Investigation, vol. 102, no. 6, pp. 1173-1182.
Estess, Pila ; DeGrendele, Heather C. ; Pascual, Virginia ; Siegelman, Mark H. / Functional activation of lymphocyte CD44 in peripheral blood is a marker of autoimmune disease activity. In: Journal of Clinical Investigation. 1998 ; Vol. 102, No. 6. pp. 1173-1182.
@article{00e44348f8dd44a8812030d9503da615,
title = "Functional activation of lymphocyte CD44 in peripheral blood is a marker of autoimmune disease activity",
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.",
keywords = "Adhesion, Arthritis, Hyaluronate, Inflammation, SLE",
author = "Pila Estess and DeGrendele, {Heather C.} and Virginia Pascual and Siegelman, {Mark H.}",
year = "1998",
month = "9",
day = "15",
language = "English (US)",
volume = "102",
pages = "1173--1182",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "6",

}

TY - JOUR

T1 - Functional activation of lymphocyte CD44 in peripheral blood is a marker of autoimmune disease activity

AU - Estess, Pila

AU - DeGrendele, Heather C.

AU - Pascual, Virginia

AU - Siegelman, Mark H.

PY - 1998/9/15

Y1 - 1998/9/15

N2 - 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.

AB - 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.

KW - Adhesion

KW - Arthritis

KW - Hyaluronate

KW - Inflammation

KW - SLE

UR - http://www.scopus.com/inward/record.url?scp=0032531108&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032531108&partnerID=8YFLogxK

M3 - Article

VL - 102

SP - 1173

EP - 1182

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 6

ER -