[Diversity of T-cell antigen receptor response in individuals with sarcoidosis].
T-lymphocytes recognize specific antigen(s) through T-cell antigen receptors (TCRs). There are two classes of TCRs: those composed of alpha beta chain dimers and those formed by gamma delta dimers. Although the pathogenesis of sarcoidosis is still unclear, participation of exogenous antigen(s) is highly suggested. To investigate the mechanism of activation and accumulation of T-lymphocytes at the sites of disease, the bias of TCRs in individuals with sarcoidosis was evaluated with respect to several points. Eighteen of 51 cases of sarcoidosis showed increase of gamma delta-TCR positive T-lymphocytes in the blood. In contrast to the blood, a low number of gamma delta T-cells and evidence of T-cell stimulation through alpha beta-TCR were observed in the lung. The TCR junctional regions of V gamma 9, V delta 2 and V beta 8 gene segments were sequenced from blood and lung T-cells of individuals with sarcoidosis and normal subjects, using RT-PCR. In normals, a huge diversity of the junctional region sequences was observed in V gamma 9, V delta 2 and V beta 8 transcripts in the blood and lung. In contrast to normal subjects, a subgroup of sarcoidosis showed an increase of V gamma 9 transcripts sharing identical sequences. Although less marked than for V gamma 9, an increase in identical junctional region sequences was also observed in V delta 2 transcripts. All junctional region sequences of V beta 8 transcripts in the blood and lung were unique, indicating polyclonal activation of T-cells through TCR beta-chain.(ABSTRACT TRUNCATED AT 250 WORDS)
Tamura
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N
Department of Respiratory Medicine, Juntendo University School of Medicine, Tokyo, Japan.
D000595:Amino Acid Sequence; D001483:Base Sequence; D015321:Gene Rearrangement; D006801:Humans; D007135:Immunoglobulin Variable Region; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D012507:Sarcoidosis / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D007135:Immunoglobulin Variable Region; D011948:Receptors, Antigen, T-Cell