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PMID: 9739051 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The Journal of clinical investigation ·Vol. 102 ·No. 6 ·1998-09-15 ·Pages 1173-82

Estess P, DeGrendele HC, Pascual V, Siegelman MH

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.

MeSH Terms
Adolescent Autoimmune Diseases/diagnosis Cell Adhesion Chemotaxis, Leukocyte Child Child, Preschool Endothelium, Vascular/immunology Female Humans Hyaluronan Receptors/blood Hyaluronic Acid/metabolism Infant Joint Diseases/immunology Lupus Erythematosus, Systemic/immunology Lymphocyte Subsets/immunology Male Palatine Tonsil/immunology Receptors, Antigen, T-Cell/immunology Rheumatic Diseases/immunology
Chemicals
Hyaluronan Receptors Receptors, Antigen, T-Cell Hyaluronic Acid
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Estess P
Laboratory of Molecular Pathology, Department of Pathology, The University of Texas Southwestern Medical Center Dallas, Dallas, TX 75235, USA.
DeGrendele H C
Pascual V
Siegelman M H
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI4235
Published
1998-09-15
Pages
1173-82
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC509100
Subset
IM
Grants
NCI NIH HHS · CA 09082 · United States
NHLBI NIH HHS · HL56746-01 · United States
NCI NIH HHS · R01 CA57571 · United States
Corrections
CommentIn
PMID: 9739040
External Links
PubMed source DOI: 10.1172/JCI4235 PMC Full Text View journal details
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