T-cell receptor gene rearrangements and expression in normal human large granular lymphocytes (LGL) and their pathological expansions |
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Authors: | Anna Pirelli Paola Allavena Alessandro Rambaldi Maria Di Bello Paola Pirovano Fedro Peccatori Alberto Mantovani |
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Institution: | (1) Lab. of Human Immunology, Institute Mario Negri , Via Eritrea 62, 20157 Milan, Italy |
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Abstract: | The lineage to which normal large granular lymphocytes/natural killer (LGL/NK) cells belong is controversial; in fact they share some surface markers and functional activities with monocytes, but also with T lymphocytes. The relationship of LGL to the T cell lineage by analysis with the T cell receptor (T-rec) gene has been investigated. Pure preparations of human LGL and their CD11+ CD8- and CD11- CD8+ subsets had the T gene in its unrearranged germline configuration. Expression of T and T genes was not detectable. The organization of T gene, which is of particular importance because it occurs early in T cell ontogeny, was also found in its germline configuration.A rare type of lymphoproliferative disorder, termed T -LPD, is characterized by expansion of cells very similar to LGL for morphology, phenotype, and functional activity. Of 17 patients with T -LPD studied for T-rec rearrangement, 15 displayed rearrangement of T and T loci and were CD3+ (14/15 had monoclonal rearrangement), while 2 cases were in germline configuration and were CD3–. Similarly to very small subsets of CD3+ LGL recently described, most T -LPD cases are CD3+ and have T-rec genes rearranged. These data suggest that either a subset of LGL or a particular step of differentiation may be related to the T cell lineage; they also demonstrate that, in contrast to previous views, most T LPD are monoclonal, presumably neoplastic, lymphoproliferative disorders.Abbreviations LGL
large granular lymphocytes
- NK
natural killer
- T-rec
T-cell receptor
- T LPD
T lymphoproliferative disease |
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Keywords: | LGL NK cells T-cell receptor genes T LPD" target="_blank">gif" alt="gamma" align="MIDDLE" BORDER="0">LPD |
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