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Preferential type 1 chemokine receptors and cytokine production of CD28^– T cells in ankylosing spondylitis

¹ Department of Internal Medicine, Innsbruck Medical University, Innsbruck, Austria
² Department of Radiology, Innsbruck Medical University, Innsbruck, Austria
³ Ludwig-Boltzmann Institute, Saalfelden, Austria
⁴ Rehabilitationszentrum-Sonderkrankenanstalt Bad-Ischl der Pensionsversicherungsanstalt, Bad Ischl, Austria

Correspondence to:
Correspondence to:
Associate Professor M Schirmer
Department of Internal Medicine, Innsbruck Medical University, A-6020 Innsbruck, Anichstrasse 35, Austria; michael.schirmer{at}uibk.ac.at

Objective: To examine serum levels of type 1 and type 2 chemokines and lymphocytic expression of chemokine receptors, and to compare the results with lymphocytic cytokine production in patients with ankylosing spondylitis (AS).

Methods: Twelve patients with AS (mean (SD) age 44.9 (14.7) years) and 27 healthy controls (46.4 (12.8) years) were enrolled into the study. The expression of chemokine receptors (CCR-5, CXCR-3, CCR-4) and cytokines (interferon (IFN), interleukin (IL)2, IL4, IL10, tumour necrosis factor (TNF)) on CD28⁺ and CD28^– T cell subtypes was analysed by a three colour FACS technique of peripheral blood samples. Serum ELISAs were performed to detect the CCR-5 ligands CCL-5, CCL-3; the CXCR-3 ligands CXCL-10, CXCL-9; and the CCR-4 ligand, CCL-17 before and after administration of the TNF blocking agent infliximab.

Results: CD4⁺CD28^– T cells had higher ratios of CXCR-3 to CCR-4 than CD4⁺CD28⁺ T cells. Both, CD4⁺ and CD8⁺CD28^– T cells of patients with AS produced more IFN, TNF, and IL10 than their CD28⁺ counterparts (p<0.05), and lacked the production of IL2 and IL4. Serum levels of CXCL-9 were increased in patients with AS to 59.2 pg/ml (34.1–730.5) compared with 32.5 pg/ml (20.0–79.5) in healthy controls (p = 0.016). The levels of both type 1 (CCL-5, CXCL-9) and type 2 chemokines (CCL-17) decreased under blockade of TNF (p<0.05).

Conclusions: The profile of chemokine receptor expression and cytokine production by CD28^– T cells suggests a type 1 immune reaction in AS, although IL10 is frequently produced by CD28^– T cells. Treatment with TNF blocking antibodies decreased both types of chemokines in patients’ sera.

Abbreviations: AS, ankylosing spondylitis; BASDAI, Bath Ankylosing Disease Activity Index; BASFI, Bath Ankylosing Spondylitis Functional Index; BASMI, Bath Ankylosing Spondylitis Metrology Index; CRP, C reactive protein; ESR, erythrocyte sedimentation rate; IFN, interferon ; IL, interleukin; PBMCs, peripheral blood mononuclear cells; PMA, phorbol 12-myristate 13-acetate; RA, rheumatoid arthritis; SpA, spondyloarthritis; TNF, tumour necrosis factor

Keywords: ankylosing spondylitis; chemokines; chemokine receptors; cytokines; tumour necrosis factor

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