Effects of preactivated autologous T lymphocytes on CD80, CD86 and CD95 expression by chronic lymphocytic leukemia B cells.
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.
Romano
Ciro
C
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.
De Fanis
Umberto
U
Sellitto
Ausilia
A
Dalla Mora
Liliana
L
Chiurazzi
Federico
F
Giunta
Riccardo
R
Rotoli
Bruno
B
Lucivero
Giacomo
G
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*
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