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The raft marker GM1 identifies functional subsets of granular lymphocytes in patients with CD3+ lymphoproliferative disease of granular lymphocytes

Leukemia volume 18, pages 771–776 (2004)Cite this article

Abstract

The raft marker GM1 is expressed at very low levels at the plasma membrane of resting T cells (GM1dull). In vitro T-cell activation induces synthesis of this lipid, which is then expressed at very high levels (GM1bright) at the membrane of activated/effector cells. By flow cytometry and confocal microscopy, we analyzed the expression and organization of GM1 in a series of 15 patients with CD3+ lymphoproliferative disease of granular lymphocytes (LDGL). We found that GM1bright GL were detectable in fresh blood samples obtained in all LDGL patients, although the range of brightly stained cells was extremely variable. This distinctive in vivo pattern has never been shown in T lymphocytes from healthy individuals or in patients with different chronic T or B lymphoproliferative disorders or active infectious diseases. The low number of cycling cells detected in LDGL patients was always included within the GM1bright GL population. Interestingly, GM1bright GL were demonstrated to contain a higher amount of IFN-γ as compared to GM1dull GL. These findings allow to distinguish subsets of GL at different levels of activation within the monoclonal CD3+ population. The GM1bright GL subset is likely to be responsible for the renewing of GL and thus for maintaining chronic proliferation.

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Acknowledgements

We thank Vincenzo Barnaba (Rome) and Tullio Pozzan (Padua) for critical reading of the manuscript and A Moretta (Genoa) for providing Xa185 mAb, Z270 mAb and BAT221 mAb. We also thank Filippo Gobbo and Davide Carollo for technical assistance. Finally, we are grateful to Mr Martin Donach for editing the manuscript. This study was supported in part by Associazione Italiana per la Ricerca sul Cancro (AIRC), Ministero dell'Istruzione dell'Università e della Ricerca (MIUR) and Consiglio Nazionale delle Ricerche (CNR), Fondo per gli Investimenti della Ricerca di Base (FIRB).

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Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, Padua University School of Medicine, Clinical Immunology Branch, University of Padua, Italy

    R Zambello, A Cabrelle, L Trentin, C Agostini & G Semenzato

  2. Department of Biomedical Sciences and Venetian Institute of Molecular Medicine (VIMM), Padua, Italy

    A Viola

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  1. R Zambello
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  2. A Cabrelle
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  3. L Trentin
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  4. C Agostini
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  5. G Semenzato
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Correspondence to G Semenzato.

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Zambello, R., Cabrelle, A., Trentin, L. et al. The raft marker GM1 identifies functional subsets of granular lymphocytes in patients with CD3+ lymphoproliferative disease of granular lymphocytes. Leukemia 18, 771–776 (2004). https://doi.org/10.1038/sj.leu.2403292

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