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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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NEOPLASIA

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

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

We investigated whether dendritic cells (DCs) play a role in favoring granular lymphocyte (GL) proliferation in patients with lymphoproliferative disease of granular lymphocytes (LDGL). The presence of in vivo circulating DCs was studied in 11 patients (5 CD3+ and 6 CD3- LDGL). Autologous immature (iDCs) and mature (mDCs) DCs generated in vitro were studied for stimulatory activity on cell proliferation of CD3+ and CD3- GLs. The topographic organization of GLs and DCs was also studied in bone marrow (BM) biopsies. Peripheral blood (PB) CD3- GLs from patients showed significant proliferative activity in the presence of iDCs and mDCs. Conversely, monoclonal CD3+ GLs were unresponsive to autologous and allogeneic PB DCs. Analysis of BM biopsies demonstrated a topographic distribution of DCs and GLs that indicates contact between the 2 cell types. On functional assays, DCs obtained from BM were more efficient than PB DCs in stimulating CD3- GLs, and surprisingly, a low but definite stimulatory effect was demonstrated also on CD3+ GLs. The putative contact between DCs and GLs 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 DCs, providing evidence for a role of DCs 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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