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

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Abstract

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 γ (IFNγ), interleukin (IL)2, IL4, IL10, tumour necrosis factor α (TNFα)) 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 TNFα 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 IFNγ, TNFα, 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 TNFα (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 TNFα blocking antibodies decreased both types of chemokines in patients’ sera.

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