Increase of peripheral CXCR3 positive T lymphocytes upon treatment of RA patients with TNF-alpha inhibitors

Abstract

Objective: To explore the regulation of factors involved in lymphocyte trafficking in patients with rheumatoid arthritis (RA) undergoing treatment with tumour necrosis factor alpha (TNF-alpha) inhibitors.

Methods: We examined 14 consecutive patients with RA according to ACR criteria prior to and during treatment with TNF-alpha 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 gamma (IFN-gamma) 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-alpha inhibition. Upon activation, up to 30% of CXCR3(+)/CD4 T cells expressed IFN-gamma, while IL-4-expressing cells were rare. There was a robust negative correlation between CXCR3(+)/CD4 T lymphocytes and DAS-28.

Conclusions: TNF-alpha 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-alpha inhibition.