The role of T cells in the immunopathogenesis of rheumatoid arthritis. New perspectives

Recent data suggest that IL-15 plays an important role in the pathogenesis of rheumatoid arthritis. In the present study, we hypothesized that elevated in the joints of rheumatoid arthritis, but not osteoarthritis, patients, IL-15 may exert its proinflammatory properties via the induction of IL-17, a cytokine known to stimulate synoviocytes to release several mediators of inflammation including IL-6, IL-8, GM-CSF and PGE2. To test this hypothesis, we first measured the levels of IL-17 and IL-15 using specific ELISA and found that synovial fluids of patients with rheumatoid arthritis, but not with osteoarthritis, contain high levels of these cytokines. A strong correlation between IL-15 and IL-17 levels in synovial fluids was observed. Among tested factors, LPS and TNF-α failed, IL-15 and IL-2 were equipotent, and PMA + ionomycin was far more efficient in the induction of IL-17 secretion by PBMCs isolated from healthy blood donors. Interestingly, synovial fluid cells, in contrast to PBMCs isolated from patients with rheumatoid arthritis, but not osteoarthritis, respond to PMA + ionomycin with much lower, comparable to IL-15-triggered IL-17 secretion. Moreover, PMA + ionomycin-triggered IL-17 secretion is completely or partially blocked in the presence of low doses of cyclosporin A or high doses of methylprednisolone, respectively. IL-15-triggered IL-17 secretion by PBMCs was completely inhibited by these drugs. Thus, our results suggest for the first time that IL-15 may represent a physiological trigger that via cyclosporin A and steroid sensitive pathways leads to the overproduction of IL-17 in the joints of rheumatoid arthritis patients.

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“…4). Taken together, the above described scenario adds a new aspect of the role of CD4 ϩ memory cells in the pathogenesis of RA (36).…”

Section: Figure 4 Production Of Il-17 By Pbmcs From Healthy Individumentioning

confidence: 73%

High Levels of IL-17 in Rheumatoid Arthritis Patients: IL-15 Triggers In Vitro IL-17 Production Via Cyclosporin A-Sensitive Mechanism

Ziolkowska¹,

Koc²,

Luszczykiewicz³

et al. 2000

The Journal of Immunology

540

402

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“…During the inflammatory process, T-helper cells (CD4), B-cells (CD19) and monocytes-macrophages would migrate into and remain in the synovium, which is a result of interaction of cellular adhesion molecules with counterligands expressed on extracellular matrix molecules (Fox, 1997;Moreland et al, 1997). It has been observed that serum levels of TNF-a, IL-6 and soluble CD4 were significantly higher in RA patients compared with 30 healthy subjects (Kuryliszyn-Moskal, 1998).…”

Section: Immune Responsesmentioning

confidence: 99%

Vitamin B6 supplementation improves pro-inflammatory responses in patients with rheumatoid arthritis

Wei

et al. 2010

Eur J Clin Nutr

110

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Background/Objectives: The purpose of this study was to investigate whether vitamin B 6 supplementation had a beneficial effect on inflammatory and immune responses in patients with rheumatoid arthritis (RA). Subjects/Methods: This was a single-blind co-intervention study performed at the Division of Allergy, Immunology and Rheumatology of Chung Shan Medical University Hospital, Taiwan. Patients were diagnosed with RA according to the 1991 American College of Rheumatology criteria for RA. Patients were randomly allocated into two groups: control (5 mg/day folic acid only; n ¼ 15) or vitamin B 6 (5 mg/day folic acid plus 100 mg/day vitamin B 6 ; n ¼ 20) for 12 weeks. Plasma pyridoxal 5 0 -phosphate (PLP), serum folate, inflammatory parameters (that is, high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), tumor necrosis factor-a (TNF-a)) and immune parameters (that is, white blood cell, total lymphocyte, T-cell (CD3), B-cell (CD19), T-helper cell (CD4), T-suppressor (CD8)) were measured on day 1 (week 0) and after 12 weeks (week 12) of the intervention. Results: In the group receiving vitamin B 6 , plasma IL-6 and TNF-a levels significantly decreased at week 12. There were no significant changes with respect to immune responses in both groups except for the percentage of total lymphocytes in the vitamin B 6 group when compared with week 0 and week 12. Plasma IL-6 level remained significantly inversely related to plasma PLP after adjusting for confounders (b ¼ À0.01, P ¼ 0.01). Conclusions: A large dose of vitamin B 6 supplementation (100 mg/day) suppressed pro-inflammatory cytokines (that is, IL-6 and TNF-a) in patients with RA.

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“…Among these immune effector cells, T cells have been considered to be the most important because the regulation of T cell activation requires antigen specificity and a great amount of cytokines released in immune responses are from T cells (1). It is clear that full activation of T cells requires the integration of two signals: one is from a T cell receptor signal and the other is from a co-stimulatory signal (2).…”

Section: Effects On T Cellsmentioning

confidence: 99%

The Immunopharmaceutical Effects and Mechanisms of Herb Medicine

Huang¹,

Lin

Liao

et al. 2008

Cell Mol Immunol

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In recent years, studies on evaluation of the therapeutic and toxic activity of herbal medicinal products became available and popular. The advances in modern biotechnology have led to discovery of many new active constituents. However, it is a constant challenge to establish the pharmacological basis for efficacy and safety of herbal medicinal products. A better understanding of the effects and bioavailability of phytopharmaceuticals can help in discovering suitable and rational therapies. In this review, we present the bioavailability studies in immune system that has been conducted for some of the more important or widely used phytopharmaceuticals. Furthermore, various new drug targets worthy of using for drug development in immunomodulating herbal medicine area and their regulatory mechanisms are also discussed. Adverse effects, drug interactions, and contraindications are also discussed which show that caution should be exercised when combining phytopharmaceuticals with chemically derived pharmaceutical components. Cellular & Molecular Immunology. 2008;5(1):23-31.

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The role of T cells in the immunopathogenesis of rheumatoid arthritis. New perspectives

Cited by 268 publications

References 121 publications

High Levels of IL-17 in Rheumatoid Arthritis Patients: IL-15 Triggers In Vitro IL-17 Production Via Cyclosporin A-Sensitive Mechanism

High Levels of IL-17 in Rheumatoid Arthritis Patients: IL-15 Triggers In Vitro IL-17 Production Via Cyclosporin A-Sensitive Mechanism

Vitamin B6 supplementation improves pro-inflammatory responses in patients with rheumatoid arthritis

The Immunopharmaceutical Effects and Mechanisms of Herb Medicine

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