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

Ann Rheum Dis. 2006 May;65(5):647-53. doi: 10.1136/ard.2005.042085. Epub 2005 Oct 11.


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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal / therapeutic use
  • CD28 Antigens / blood*
  • Chemokines / blood
  • Cytokines / biosynthesis*
  • Enzyme-Linked Immunosorbent Assay / methods
  • Female
  • Humans
  • Infliximab
  • Male
  • Middle Aged
  • Receptors, Chemokine / blood*
  • Spondylitis, Ankylosing / drug therapy
  • Spondylitis, Ankylosing / immunology*
  • T-Lymphocyte Subsets / immunology*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors


  • Antibodies, Monoclonal
  • CD28 Antigens
  • Chemokines
  • Cytokines
  • Receptors, Chemokine
  • Tumor Necrosis Factor-alpha
  • Infliximab