title: Effects of preactivated autologous T lymphocytes on CD80, CD86 and CD95 expression by chronic lymphocytic leukemia B cells.
abstract: Profound immune dysfunction is a constant feature in B-cell chronic lymphocytic leukemia (B-CLL) patients. Immunological abnormalities include hypogammaglobulinemia, impaired immunoglobulin class switching and diminished germinal center formation. This state of immune suppression renders B-CLL patients highly susceptible to infections, which contribute greatly to morbidity and mortality in this disease. Impaired T cell function in B-CLL is well-documented and has been suggested to result from inhibitory effects exerted by malignant B lymphocytes. Because the presence of leukemic cells may represent a major obstacle to efficient T cell activation, T lymphocytes were separated from CLL B cells, stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin for 4h, and then cocultured with autologous leukemic B cells both at a 1:1 ratio or at the same ratio as in vivo for 24-40 h. CLL B cell expression of CD86 and CD95 was markedly upregulated using this approach, whereas CD80 expression was augmented only in a minority of patients; these effects were partially preserved even when preactivated T cells were rechallenged with CLL B cells at the same low T/B cell ratio as that observed in vivo. Finally, CD80 upregulation on CLL B cells appeared to be mainly dependent on CD40L-mediated stimulation, whereas CD86 and CD95 expression was efficiently augmented by soluble factors released by preactivated T lymphocytes. In conclusion, efficient activation of T lymphocytes in B-CLL may be achieved which, in turn, may result in enhanced antigen-presenting capacity and susceptibility to apoptosis of leukemic cells via CD86 and CD95 upregulation, respectively.
authors.affiliation: Division of Internal Medicine, Allergy and Clinical Immunology, Department of Gerontology, Geriatrics, and Metabolic Diseases, Second University of Naples School of Medicine, Piazza L. Miraglia, 3, 80138 Naples, Italy.
authors.forename: Ciro
authors.initials: C
authors.lastname: Romano
authors.forename: Umberto
authors.initials: U
authors.lastname: De Fanis
authors.forename: Ausilia
authors.initials: A
authors.lastname: Sellitto
authors.forename: Liliana
authors.initials: L
authors.lastname: Dalla Mora
authors.forename: Federico
authors.initials: F
authors.lastname: Chiurazzi
authors.forename: Riccardo
authors.initials: R
authors.lastname: Giunta
authors.forename: Bruno
authors.initials: B
authors.lastname: Rotoli
authors.forename: Giacomo
authors.initials: G
authors.lastname: Lucivero
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D018122:B7-1 Antigen / Q000378:metabolism*; D051940:B7-2 Antigen; D023201:CD40 Ligand / Q000378:metabolism; D018920:Coculture Techniques; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D015759:Ionomycin / Q000494:pharmacology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015854:Up-Regulation; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D008562:Membrane Glycoproteins; D019014:fas Receptor; D023201:CD40 Ligand; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate