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.

Abstract

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.

CONCLUSION:

. 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.

• Authors: Liping Pang, Lisha Wang, Talin Suo, Huiqin Hao, Xianfeng Fang, Junying Jia, Feng Huang, Jie Tang
• Journal: The Journal of rheumatology (J Rheumatol) Vol. 35 Issue 11 Pg. 2220-8 (Nov 2008) ISSN: 0315-162X [Print] Canada
• PMID: 19004053 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antirheumatic Agents
• Histocompatibility Antigens Class II
• Immunoglobulin G
• Interleukin-2
• Placebos
• Receptors, Interleukin-2
• Receptors, Tumor Necrosis Factor
• Tumor Necrosis Factor-alpha
• Interferon-gamma
• Etanercept

Topics

• Adult
• Antirheumatic Agents (administration & dosage)
• Cell Division (drug effects, immunology)
• Dendritic Cells (cytology, drug effects, metabolism)
• Enzyme-Linked Immunosorbent Assay
• Etanercept
• Female
• Histocompatibility Antigens Class II (metabolism)
• Humans
• Immunoglobulin G (administration & dosage)
• Interferon-gamma (metabolism)
• Interleukin-2 (metabolism)
• Lymphocyte Count
• Male
• Placebos
• Receptors, Interleukin-2 (blood)
• Receptors, Tumor Necrosis Factor (administration & dosage)
• Spondylitis, Ankylosing (drug therapy, immunology)
• T-Lymphocytes (cytology, drug effects, metabolism)
• T-Lymphocytes, Regulatory (cytology, drug effects, immunology)
• Treatment Outcome
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, metabolism)
• Young Adult