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Dynamic T‐lymphocyte Chemokine Receptor Expression Induced by Interferon‐beta Therapy in Multiple Sclerosis
Author(s) -
Krakauer M.,
Sorensen P. S.,
Khademi M.,
Olsson T.,
Sellebjerg F.
Publication year - 2006
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.2006.01788.x
Subject(s) - ccl5 , ccl17 , c c chemokine receptor type 7 , cxcl10 , ccl13 , cxcr3 , cxcl9 , chemokine receptor ccr5 , chemokine , ccr4 , chemokine receptor , cc chemokine receptors , immunology , cx3cl1 , biology , t cell , inflammation , il 2 receptor , immune system
Treatment with interferon (IFN)‐ β reduces clinical disease activity in multiple sclerosis (MS). Using flow cytometry, an enzyme‐linked immunosorbent assay and a real‐time polymerase chain reaction, we studied in vivo IFN‐ β ‐induced effects on CD4 + T‐lymphocyte chemokine receptor expression as these influence central nervous system (CNS) transmigration and inflammation. At ‘steady state’ (≥1 day after the most recent IFN‐ β injection), IFN‐ β treatment increased CD4 + T‐cell surface expression of CC chemokine receptor (CCR)4, CCR5 and CCR7 after 3 months of treatment, whereas that of CXC chemokine receptor (CXCR)3 was unaltered. Conversely, at 9–12 h after the most recent IFN‐ β injection, CCR4, CCR5 and CCR7 expressions were unaltered, while CXCR3 expression was reduced. CD4 + T‐cell surface expression of CCR4 was significantly lower in untreated MS patients compared with healthy volunteers. Of the plasma chemokines, only CXCL10 was increased by IFN‐ β treatment; CCL3, CCL4, CCL5 and CXCL9 were unaltered. CCR5 mRNA expression in blood mononuclear cells correlated with the expression of T‐helper type 1 (Th1)‐associated genes whereas CCR4 and CCR7 mRNA expression correlated with Th2 and immunoregulatory genes. In conclusion, IFN‐ β treatment caused ‘steady‐state’ increases of several chemokine receptors relevant for CD4 + T‐lymphocyte trafficking and function, possibly facilitating lymphocyte migration into the CNS. An important therapeutic effect of IFN‐ β treatment may be the normalization of a decreased Th2‐related CD4 + T‐cell CCR4 expression in MS patients. Surface chemokine receptor expression and CXCL10 varied according to the timing of blood sampling in relation to the most recent IFN‐ β injection. Thus, it is imperative to distinguish acute effects of IFN‐ β from steady‐state effects.