Aberrant expression of adhesion molecules by Sézary cells: Functional consequences under physiologic shear stress conditions

Samuel T Hwang, D. J. Fitzhugh

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Although aberrations in adhesion molecule expression by lymphoma cells have been reported, the functional consequences of these changes are unclear. Herein, we report a patient with Sézary syndrome whose malignant peripheral blood T cells were TCRVβ17+. Malignant T cell adhesion molecule abnormalities included an 80% downregulation of LFA-1 compared with normal controls and no detectable expression of α4 integrin. Under shear stress conditions, malignant T cells failed to arrest on recombinant ICAM-1 in the presence of chemokines and displayed an 80% decrease in the ability to arrest on TNF-α activated dermal microvascular endothelial cells compared with normal CD4+ memory T cells. Cutaneous lymphocyte-associated antigen expression was detected in ∼25% of malignant T cells in the peripheral blood, but was substantially less than this in TCRVβ17+ T cells in the dermis. By contrast, > 95% of malignant T cells in peripheral blood expressed L-selectin (CD62L), and L-selectin ligand was detected in dermal blood vessels at affected skin sites. Compared with normal CD4+, malignant T cells attached and rolled 6-fold more efficiently on L-selectin ligand (p < 0.0001). Thus, despite aberrant expression of LFA-1 and functional defects in the ability to arrest on activated endothelial cells, malignant T cells in this patient entered skin and produced significant clinical disease. We propose a mechanism by which the upregulated expression of L-selectin and L-selectin ligands may partially compensate for altered LFA-1 function.

Original languageEnglish (US)
Pages (from-to)466-470
Number of pages5
JournalJournal of Investigative Dermatology
Volume116
Issue number3
DOIs
StatePublished - 2001
Externally publishedYes

Keywords

  • Adhesion molecules
  • Integrin
  • L-selectin
  • Lymphoma

ASJC Scopus subject areas

  • Dermatology

Fingerprint Dive into the research topics of 'Aberrant expression of adhesion molecules by Sézary cells: Functional consequences under physiologic shear stress conditions'. Together they form a unique fingerprint.

  • Cite this