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 (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.
Duftner
C
C
Department of Internal Medicine, Innsbruck Medical University, A-6020 Innsbruck, Anichstrasse 35, Austria.
Dejaco
C
C
Kullich
W
W
Klauser
A
A
Goldberger
C
C
Falkenbach
A
A
Schirmer
M
M
D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D018106:CD28 Antigens / Q000097:blood*; D018925:Chemokines / Q000097:blood; D016207:Cytokines / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D019707:Receptors, Chemokine / Q000097:blood*; D013167:Spondylitis, Ankylosing / Q000188:drug therapy / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D018925:Chemokines; D016207:Cytokines; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab