Abstract | OBJECTIVE: METHODS: MPO-specific T cells were quantified by enzyme-linked immunospot assay with additional Treg cell depletion or exogenous interleukin-2. Serum tryptophan and its metabolites were measured. In vivo blockade of indoleamine 2,3-dioxygenase (IDO) was performed, and its effect on MPO reactivity was assessed. RESULTS: During disease remission, MPO-specific interferon-gamma-producing T cell frequencies were comparable with those found in healthy controls and significantly lower than those found in patients with acute disease. CD4+CD25+ regulatory cells did not play a role in maintaining these low MPO-specific T cell frequencies, since depletion of Treg cells did not augment MPO-specific responses, and FoxP3 levels were diminished in patients compared with controls. Treg cell function, however, was comparable in patients and controls, suggesting numerical rather than functional deficiency. We found diminished serum tryptophan levels and elevated levels of its metabolite kynurenine in patients with MPO AAV as compared with controls. To confirm the effect of tryptophan degradation on MPO responses in vivo, we inhibited degradation in MPO-immunized WKY rats and found greater immune responsiveness to MPO and a tendency to more severe glomerulonephritis. CONCLUSION: Our findings indicate that MPO-specific T cell frequencies are regulated during disease remission in association with tryptophan degradation. The tryptophan regulatory pathway is induced during active disease and persists during disease remission.
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Authors | Konstantia-Maria Chavele, Deepa Shukla, Tracey Keteepe-Arachi, Judith Anna Seidel, Dietmar Fuchs, Charles D Pusey, Alan D Salama |
Journal | Arthritis and rheumatism
(Arthritis Rheum)
Vol. 62
Issue 5
Pg. 1539-48
(May 2010)
ISSN: 1529-0131 [Electronic] United States |
PMID | 20155828
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Antineutrophil Cytoplasmic
- Biomarkers
- Immunosuppressive Agents
- Kynurenine
- Neopterin
- Tryptophan
- Peroxidase
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Topics |
- Acute Disease
- Aged
- Antibodies, Antineutrophil Cytoplasmic
(immunology)
- Biomarkers
(blood)
- Enzyme-Linked Immunosorbent Assay
- Female
- Humans
- Immunosuppressive Agents
(therapeutic use)
- Kynurenine
(blood)
- Lymphocyte Count
- Male
- Middle Aged
- Neopterin
(blood)
- Peroxidase
(metabolism)
- Remission Induction
- T-Lymphocytes, Regulatory
(enzymology, immunology)
- Tryptophan
(blood)
- Vasculitis
(drug therapy, immunology, metabolism)
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