Tumor necrosis factor-alpha blockade leads to decreased peripheral T cell reactivity and increased dendritic cell number in peripheral blood of patients with ankylosing spondylitis.
OBJECTIVE
To study the effect of tumor necrosis factor-alpha (TNF-alpha) antagonist (etanercept) treatment on the peripheral T cell reactivity of patients with ankylosing spondylitis (AS).


METHODS
Peripheral blood mononuclear cells were collected from 40 patients with AS at baseline, after 2 and 6 weeks of etanercept treatment or placebo treatment, and from healthy controls. The number of cells secreting various cytokines was detected by enzyme linked immunospot. Serum soluble interleukin 2 (IL-2) receptor level was measured by ELISA. T cell proliferation was assayed with the WST-1 live cell-staining method. The myeloid dendritic cell (mDC) and regulatory T cell (Treg) levels were analyzed by fluorescence activated cell sorting.


RESULTS
. After 2 and 6 weeks of etanercept treatment, the number of TNF-alpha-secreting monocytes decreased. Although the T cell proliferation rate remained stable, the number of T cells secreting IL-2 and interferon-gamma under anti-CD3/anti-CD28 stimulation was significantly decreased. The level of serum soluble IL-2R (sIL-2R), a T cell activation marker, also declined. The changes in T cell reactivity were correlated with a significant increase in MHC Class II-positive mDC cells in circulation. An increase in Treg cell numbers was also observed.


CONCLUSIONS
. The anti-TNF-alpha therapy blockaded MHC Class II-positive mDC maturation, enhanced regulatory T cell levels, and suppressed the functions of effector T cells. The reduced T cell reactivity could contribute to the efficacy of the TNF-alpha antagonist therapy in patients with AS.
Pang
Liping
L
National Laboratory of Biomacromolecules, Center for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, China.
Wang
Lisha
L
Suo
Talin
T
Hao
Huiqin
H
Fang
Xianfeng
X
Jia
Junying
J
Huang
Feng
F
Tang
Jie
J
D000328:Adult; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D000068800:Etanercept; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage*; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D018655:Lymphocyte Count; D008297:Male; D010919:Placebos; D015375:Receptors, Interleukin-2 / Q000097:blood; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage*; D013167:Spondylitis, Ankylosing / Q000188:drug therapy* / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D055815:Young Adult
D018501:Antirheumatic Agents; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D007376:Interleukin-2; D010919:Placebos; D015375:Receptors, Interleukin-2; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D000068800:Etanercept