sq-23377 and Multiple-Sclerosis--Relapsing-Remitting

The purpose of the current study is to examine the surface expression of chemokine receptors and the chemotaxis toward the respective chemokines of glatiramer acetate (GA)-specific CD4(+) T cells isolated from the blood and the cerebrospinal fluid (CSF) of a multiple sclerosis (MS) patient. Four clones were selected, two isolated from the peripheral blood and two from the CSF. CCR4 and CXCR3 were expressed on all four clones. Both blood-derived clones also expressed CCR5 and, to a lesser extent, CCR6. Similarly, one CSF clone expressed CCR5 and CCR6. In contrast, CCR1, CCR2, CCR3, CCR7, CCR9, CCR10, CXCR1, CXCR4, CXCR5, CXCR6, and CCR6 were either expressed on few cells or were not expressed at all on all four clones examined. The expression of chemokine receptors was corroborated with the ability of the cells to respond chemotactically to the corresponding chemokines, CCL5/RANTES, CCL20/MIP-3α, CCL22/MDC and CXCL10/IP-10. Both the receptor expression and chemotaxis were reduced upon activation with PMA and ionomycin. The shared expression of chemokine receptors and the migration patterns suggest that GA-reactive cells have migrated from the blood into the CSF, and that local reactivation within the inflamed CSF may downregulate the expression of chemokine receptors and hence impede their migration intrathecally. The results may also explain the beneficial synergistic effects of combining immunosuppressive drugs with GA in MS patients.

Topics: Adult; Blood; CD4-Positive T-Lymphocytes; Cell Movement; Cells, Cultured; Cerebrospinal Fluid; Chemokines; Chemotaxis, Leukocyte; Flow Cytometry; Gene Expression; Glatiramer Acetate; Humans; Inflammation; Ionomycin; Lymphocyte Activation; Male; Multiple Sclerosis, Relapsing-Remitting; Peptides; Receptors, CCR4; Receptors, CCR5; Receptors, CCR6; Receptors, CXCR3; Signal Transduction; Tetradecanoylphorbol Acetate