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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.
Submitted May 17, 2005
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 * 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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