title: Phenotypic and functional analyses of dendritic cells in patients with lymphoproliferative disease of granular lymphocytes (LDGL).
abstract: 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.
authors.affiliation: Padua University School of Medicine, Department of Clinical and Experimental Medicine, Hematology and Clinical Immunology Branch, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Zambello
authors.forename: Tamara
authors.initials: T
authors.lastname: Berno
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cannas
authors.forename: Ilenia
authors.initials: I
authors.lastname: Baesso
authors.forename: Gianni
authors.initials: G
authors.lastname: Binotto
authors.forename: Emanuela
authors.initials: E
authors.lastname: Bonoldi
authors.forename: Pierantonio
authors.initials: P
authors.lastname: Bevilacqua
authors.forename: Marta
authors.initials: M
authors.lastname: Miorin
authors.forename: Monica
authors.initials: M
authors.lastname: Facco
authors.forename: Livio
authors.initials: L
authors.lastname: Trentin
authors.forename: Carlo
authors.initials: C
authors.lastname: Agostini
authors.forename: Gianpietro
authors.initials: G
authors.lastname: Semenzato
mesh_terms: D017252:CD3 Complex / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology*; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D005434:Flow Cytometry; D006098:Granulocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008232:Lymphoproliferative Disorders / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D017252:CD3 Complex