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

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 gamma (IFN gamma), interleukin (IL) 2, IL4, IL10, tumour necrosis factor alpha (TNF alpha)) 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 alpha 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 gamma, TNF alpha, 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 alpha ( 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 alpha blocking antibodies decreased both types of chemokines in patients' sera.