Clinical–Liver, Pancreas, and Biliary TractQuantitation and phenotypic analysis of natural killer T cells in primary biliary cirrhosis using a human CD1d tetramer☆,☆☆
Section snippets
Tetrameric human CD1d-α-GalCer complex
α-GalCer was synthesized and kindly provided by the Pharmaceutical Research Laboratory of Kirin Brewery Co.18 Then, tetrameric human CD1d complexes loaded with α-GalCer and control unloaded hCD1d tetramers were prepared. First, a human CD1d heavy chain was PCR amplified and cloned into the SalI and BamHI sites of the previously described mouse CD1/β2-microglobulin (β2m) expression vector pBacP10pH (gift of J. Kappler; National Jewish Center, Denver, CO), thereby replacing the mouse CD1d heavy
Detection of hCD1d tetramer-binding cells in PBMCs
Our initial attempts were focused on defining the specific peripheral lymphocytes stained with hCD1d tetramer loaded with α-GalCer. Thus, PBMCs from 28 healthy individuals were stained with FITC-labeled anti-CD3 antibody and PE-labeled hCD1d tetramer loaded with α-GalCer (hCD1d tetramer) or an “empty” hCD1d tetramer not complexed with α-GalCer. A distinct population of CD3+ lymphocytes positively stained with α-GalCer loaded hCD1d tetramer was detected in all 28 samples, at a frequency of 0.07%
Discussion
Several lines of evidence suggest that NKT cells are implicated in human as well as murine models of autoimmune diseases. Nonobese diabetic (NOD) mice are numerically and functionally deficient in NKT cells in the thymus24, 25 and, to a lesser extent, in the periphery26 well before the onset of diabetes.27 A quantitative defect in NKT cells has also been reported in other autoimmune mouse models such as lpr/lpr and NZB and NZB/NZW F1 mice.28, 29
Transfer of double-negative NKT thymocytes
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Address requests for reprints to: M. Eric Gershwin, M.D., Division of Rheumatology, Allergy, and Clinical Immunology, University of California at Davis School of Medicine, TB 192, One Shields Avenue, Davis, California 95616. e-mail: [email protected]; fax: (530) 752-4669.
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Supported by grants DK39588 (to M. E. G.) and AI45053 (to M. K.) from the National Institutes of Health.