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Quantitation and phenotypic analysis of natural killer T cells in primary biliary cirrhosis using a human CD1d
Hiroto Kita1, Olga V Naidenko, Mitchell Kronenberg
1Division of Rheumatology, Allergy, and Clinical Immunology, University of California, Davis, CA 95616, USA.
Background & Aims:
Natural killer T (NKT) cells are a subset of lymphocytes incriminated in playing an important role in the modulation of the innate immune response and the development of autoimmunity. However, there have been only limited studies attempting to quantitate the number of NKT cells in autoimmune disease, particularly because of difficulties associated with definition of this subpopulation.
Methods:
We used a human CD1d (hCD1d) tetramer produced by a baculovirus expressing recombinant CD1d protein complexed with alpha-galactosylceramide (alpha-GalCer) and quantitated hCD1d tetramer reactive cells in blood and liver from controls and patients with primary biliary cirrhosis (PBC).
Results:
The majority of CD1d-alphaGalCer-restricted NKT cells were positive for TCR Valpha24 and Vbeta11. There was a distinct CD4- CD8+ population within the CD1d-alphaGalCer-restricted NKT cells in addition to the CD4- CD8- and CD4+ CD8- population. The frequency of CD1d-alphaGalCer-restricted NKT cells was similar between blood and liver in healthy individuals. In contrast, the frequency of CD1d-alphaGalCer-restricted NKT cells in the liver was significantly higher than in the blood of PBC patients. The frequency of CD1d-alpha-GalCer-restricted NKT cells in the liver was also significantly higher in PBC patients than in healthy individuals.
Conclusions:
The frequency and function of such cells should be studied not only in blood but also in the target organ of the autoimmune disease. Selective enrichment of CD1d-alphaGalCer-restricted NKT cells at the site of inflammation is observed in PBC, suggesting a role of these cells in the development of PBC.
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