title: Dendritic cells from chronic lymphocytic leukemia patients are normal regardless of Ig V gene mutation status.
abstract: Patients with B-type chronic lymphocytic leukemia (B-CLL) segregate into 2 subgroups based on the mutational status of the immunoglobulin (Ig) V genes and the patients in these subgroups follow very different clinical courses. To examine whether dendritic cells (DCs) generated from CLL patients can be candidates for immune therapy, we compared the phenotypic and functional capacities of DCs generated from patients of the 2 CLL subgroups (normal age-matched subjects [normal-DCs]). Our data show that immature DCs from B-CLL patients (B-CLL-DCs) have the same capacity to take up antigen as those from normal controls. Furthermore, B-CLL-DCs generated from the 2 CLL subgroups up-regulated MHC-II, CD80, CD86, CD83, CD40, and CD54 and down-regulated CD206 in response to stimulation with a cocktail of cytokines (CyC) and secreted increased levels of tumor necrosis factor alpha, interleukin (IL)-8, IL-6, IL-12 (p70), and RANTES in a manner typical of mature normal-DCs. Interestingly, CD54 was significantly more up-regulated by CyC in B-CLL-DCs compared with normal-DCs. Except for CD54, no significant differences in surface molecule expression were observed between normal-DCs and B-CLL-DCs. B-CLL-DCs from both subgroups, including 6 patients with VH1-69, that usually fare poorly, presented tetanus toxoid to autologous T cells in vitro similar to normal- DCs. Our data show that DCs generated from the B-CLL subgroup with unmutated Ig V genes are functionally normal. These results are very promising for the use of DCs from patients with poor prognosis for immunotherapy.
authors.affiliation: The Laboratory of Experimental Immunology, Institute for Medical Research, North Shore-LIJ Health System, Manhasset, New York, USA. dmessmer@ucsd.edu
authors.forename: Davorka
authors.initials: D
authors.lastname: Messmer
authors.forename: Gloria
authors.initials: G
authors.lastname: Telusma
authors.forename: Tarun
authors.initials: T
authors.lastname: Wasil
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Messmer
authors.forename: Steven
authors.initials: S
authors.lastname: Allen
authors.forename: Kanti R
authors.initials: KR
authors.lastname: Rai
authors.forename: Nicholas
authors.initials: N
authors.lastname: Chiorazzi
mesh_terms: D000368:Aged; D000941:Antigens / Q000378:metabolism; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D004705:Endocytosis; D005260:Female; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D013601:T-Lymphocytes / Q000378:metabolism; D013745:Tetanus Toxoid / Q000494:pharmacology
chemical_list: D000941:Antigens; D016207:Cytokines; D007135:Immunoglobulin Variable Region; D013745:Tetanus Toxoid