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Blood, 1 December 2005, Vol. 106, No. 12, pp. 3926-3931.
Prepublished online as a Blood First Edition Paper on August 9, 2005; DOI 10.1182/blood-2005-05-1972.


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Submitted May 17, 2005
Accepted July 28, 2005

Phenotypic and functional analyses of dendritic cells in patients with lymphoproliferative disease of granular lymphocytes (LDGL)

Renato Zambello, Tamara Berno, Giovanna Cannas, Ilenia Baesso, Gianni Binotto, Emanuela Bonoldi, Pierantonio Bevilacqua, Marta Miorin, Monica Facco, Livio Trentin, Carlo Agostini, and Gianpietro Semenzato*

Department of Clinical and Experimental Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine, University of Padua, Padova, Italy; Venetian Institute of Molecular Medicine (VIMM), Padova, Italy; Istituto Oncologico Veneto (IOV), Padova, Italy
Pathology Department, San Bortolo Hospital, Vicenza, Italy

* Corresponding author; email: g.semenzato{at}unipd.it.

We investigated whether dendritic cells (DC) play a role in favouring granular lymphocytes (GL) proliferation in LDGL patients. The presence of in vivo circulating DC was studied in 11 patients (5 CD3+ and 6 CD3- LDGL). Autologous immature (iDC) and mature (mDC) DC generated in vitro were studied for stimulatory activity on cell proliferation of CD3+ and CD3- GL. The topographic organization of GL and DC was also studied in bone marrow (BM) biopsies. PB CD3- GL from patients showed significant proliferative activity in the presence of iDC and mDC. Conversely, monoclonal CD3+ GL were unresponsive to autologous and allogeneic PB DC. Analysis of BM biopsies demonstrated a topographic distribution of DC and GL that indicates contact between the two cell types. On functional assays, DC obtained from BM were more efficient than PB DC in stimulating CD3- GL, and surprisingly, a low but definite stimulatory effect was demonstrated also on CD3+ GL. The putative contact between DC and GL in the BM and, more crucial, the proliferative response of discrete GL populations to DC stimulation suggest the presence of a specific antigen within BM DC, providing evidence for a role of DC in the pathogenesis of LDGL.


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R. Zambello and G. Semenzato
Large granular lymphocyte disorders: new etiopathogenetic clues as a rationale for innovative therapeutic approaches
Haematologica, October 1, 2009; 94(10): 1341 - 1345.
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