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

Although aberrations in adhesion molecule expression by lymphoma cells have been reported, the functional consequences of these changes are unclear. H erein, we report a patient with Sezary syndrome whose malignant peripheral blood T cells were TCRV beta 17(+). Malignant T cell adhesion molecule abno rmalities included an 80% downregulation of LFA-1 compared with normal cont rols and no detectable expression of alpha4 integrin. Under shear stress co nditions, malignant T cells failed to arrest on recombinant ICAM-1 in the p resence of chemokines and displayed an 80% decrease in the ability to arres t on TNF-alpha activated dermal microvascular endothelial cells compared wi th normal CD4(+) memory T cells. Cutaneous lymphocyte-associated antigen ex pression was detected in similar to 25% of malignant T cells in the periphe ral blood, but was substantially less than this in TCRV beta 17(+) 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(+), malignan t 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 def ects in the ability to arrest on activated endothelial cells, malignant T c ells 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.