Increase of peripheral CXCR3 positive T lymphocytes upon treatment of RA patients with TNF-alpha inhibitors.
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.
Aeberli
D
D
Department of Rheumatology and Clinical Immunology/Allergology, University Hospital, CH-3010 Bern, Switzerland.
Seitz
M
M
Jüni
P
P
Villiger
P M
PM
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D000069285:Infliximab; D007371:Interferon-gamma / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D017493:Leukocyte Common Antigens / Q000276:immunology; D008297:Male; D008875:Middle Aged; D054398:Receptors, CCR4; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000032:analysis / Q000276:immunology*; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; C515354:CCR4 protein, human; C515187:CXCR3 protein, human; D007074:Immunoglobulin G; D054398:Receptors, CCR4; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma; D000069285:Infliximab; D017493:Leukocyte Common Antigens; D000068800:Etanercept