PMID- 19917167
OWN - NLM
STAT- MEDLINE
DCOM- 20100330
LR  - 20170112
IS  - 0392-856X (Print)
IS  - 0392-856X (Linking)
VI  - 27
IP  - 5
DP  - 2009 Sep-Oct
TI  - Characterization of autoreactive T-cell clones to myeloperoxidase in patients 
      with microscopic polyangiitis and healthy individuals.
PG  - 826-9
AB  - OBJECTIVE: To characterize autoreactive T cells against myeloperoxidase (MPO) by 
      generating antigen-specific T-cell clones from patients with microscopic 
      polyangiitis (MPA) and healthy individuals. METHODS: Peripheral blood T cells 
      from five patients with MPA and MPO-anti-neutrophil cytoplasmic antibodies 
      (ANCAs) and from three healthy donors were used to establish MPO-specific T-cell 
      clones by repeated stimulation with recombinant MPO fragments, followed by 
      limiting dilution. The MPO-specific T-cell clones were subjected to analyses for 
      CD4/CD8 phenotype, human leukocyte antigen (HLA) class II restriction, T-cell 
      receptor (TCR) Beta-chain gene usage, complementarity-determining region 3 (CDR3) 
      amino acid sequences, and cytokine expression profiles. RESULTS: We successfully 
      generated seven MPO-specific T-cell clones, five from the patients and two from 
      healthy donors. Two clones recognized the light chain of MPO and five recognized 
      the heavy chain. All the clones were HLA-DR-restricted CD4(+)CD8(-) helper T 
      cells. The T-cell clones shared TCR Beta CDR3 amino acid motifs, depending on 
      their MPO epitope: AGXiXiN was used by clones recognizing the light chain and 
      TGXiS or QGXiE by those recognizing the heavy chain, whether the cells were 
      derived from MPA patients or healthy subjects. However, the cytokine expression 
      profiles of the patients' clones were skewed towards the Th1 phenotype, whereas 
      the healthy individuals' clones remained Th0. CONCLUSIONS: We have characterized 
      MPO-reactive T cells in detail. This information may be useful for elucidating 
      the mechanism of ANCA production and for developing selective therapeutic 
      strategies for MPO-ANCA-associated vasculitis.
FAU - Seta, N
AU  - Seta N
AD  - Department of Internal Medicine, Keio University School of Medicine, Tokyo, 
      Japan.
FAU - Kobayashi, S
AU  - Kobayashi S
FAU - Hashimoto, H
AU  - Hashimoto H
FAU - Kuwana, M
AU  - Kuwana M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Italy
TA  - Clin Exp Rheumatol
JT  - Clinical and experimental rheumatology
JID - 8308521
RN  - 0 (Autoantigens)
RN  - 0 (Cytokines)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - EC 1.11.1.7 (Peroxidase)
SB  - IM
MH  - Autoantigens/*immunology
MH  - Autoimmunity
MH  - Case-Control Studies
MH  - Cell Line
MH  - Cytokines/metabolism
MH  - Humans
MH  - Microscopic Polyangiitis/*immunology
MH  - Peroxidase/*immunology
MH  - Receptors, Antigen, T-Cell/immunology
MH  - T-Lymphocytes, Helper-Inducer/*immunology/metabolism
EDAT- 2009/11/18 06:00
MHDA- 2010/03/31 06:00
CRDT- 2009/11/18 06:00
PHST- 2009/11/18 06:00 [entrez]
PHST- 2009/11/18 06:00 [pubmed]
PHST- 2010/03/31 06:00 [medline]
AID - 2800 [pii]
PST - ppublish
SO  - Clin Exp Rheumatol. 2009 Sep-Oct;27(5):826-9.