Rheumatology Advance Access originally published online on October 27, 2004
Rheumatology 2005 44(2):172-175; doi:10.1093/rheumatology/keh437
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Rheumatology Vol. 44 No. 2 © British Society for Rheumatology 2004; all rights reserved
Increase of peripheral CXCR3 positive T lymphocytes upon treatment of RA patients with TNF-
inhibitors
1 Department of Rheumatology and Clinical Immunology/Allergology, University Hospital, 2 Division of Epidemiology and Biostatistics, Department of Social and Preventive Medicine, University of Berne, Berne, Switzerland and 3 MRC Health Services Research Collaboration, Department of Social Medicine, University of Bristol, Bristol, UK.
Correspondence to: P. M. Villiger, Department of Rheumatology and Clinical Immunology/Allergology; University Hospital, CH-3010 Bern, Switzerland. E-mail: peter.villiger{at}insel.ch
Objective. To explore the regulation of factors involved in lymphocyte trafficking in patients with rheumatoid arthritis (RA) undergoing treatment with tumour necrosis factor 
(TNF-) inhibitors.
Methods. We examined 14 consecutive patients with RA according to ACR criteria prior to and during treatment with TNF- inhibitors (seven etanercept, seven infliximab) and determined disease activity using the Disease Activity Score (DAS-28). Peripheral blood mononuclear cells were isolated before and after 6 and 14 weeks of treatment and analysed immediately for CD3, CD4 and CD8, expression of chemokine receptors CXCR3 and CCR4, CD45RO phenotype and for expression of interferon 
(IFN-) and interleukin 4 (IL-4) using four-colour flow cytometry.
Results. We found significant increases in CD4 and CD8 T lymphocytes expressing CXCR3 after 6 and 14 weeks. The overall proportion of T lymphocytes expressing CCR4 appeared unchanged. More than half of peripheral CD4 T lymphocytes showed a memory phenotype (CD45RO), with a non-significant increase under TNF- inhibition. Upon activation, up to 30% of CXCR3+/CD4 T cells expressed IFN-, while IL-4-expressing cells were rare. There was a robust negative correlation between CXCR3+/CD4 T lymphocytes and DAS-28.
Conclusions. TNF- inhibition with infliximab and etanercept results in sustained accumulation of CXCR3 positive T lymphocytes in the peripheral blood of RA patients. This suggests altered lymphocyte trafficking during TNF- inhibition.
KEY WORDS: TNF, Etanercept, Infliximab, CXCR3, Th1, T lymphocyte, Disease activity score, Inhibition
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