Idiotype-pulsed dendritic cells are able to induce antitumoral cytotoxic CD8 cells in chronic lymphocytic leukaemia.
Idiotypic structures of immunoglobulins from malignant B cells constitute tumour-specific antigens, though the function of immunoglobulin-specific CD8+ T cells in disease control and rejection remains unclear. We have studied five cases of B chronic lymphocytic leukaemia patients affected with indolent (three patients) or aggressive (two patients) disease. We showed that CD8+ T cells with major histocompatibility complex class I-restricted cytotoxicity against autologous tumour B cells could be generated following repeated stimulations with idiotype-pulsed dendritic cells in vitro. CD8+ T-cell lines were able to upregulate CD69 expression and to release interferon (IFN)-gamma upon contact with the autologous B cells, though cytolytic activity was only substantiated for patients with indolent disease. The failure of cytolytic activity in patients with aggressive disease may be explained by a skewed maturation of memory CD8 cells.
Vuillier
Françoise
F
Unité d'Immuno-Hématologie et d'Immunopathologie, Institut Pasteur, Paris, France. vuillier@pasteur.fr
Maloum
Karim
K
Thomas
Elaine K
EK
Magnac
Christian
C
Dumas
Gérard
G
Payelle-Brogard
Béatrice
B
Oppezzo
Pablo
P
Dighiero
Guillaume
G
Scott-Algara
Daniel
D
D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D015395:Histocompatibility Antigens Class I; D006801:Humans; D007075:Immunoglobulin M / Q000008:administration & dosage / Q000276:immunology; D007156:Immunologic Memory; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000276:immunology; D037181:Lectins, C-Type; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology / Q000628:therapy*; D008213:Lymphocyte Activation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D007075:Immunoglobulin M; D007371:Interferon-gamma; D037181:Lectins, C-Type; D000099192:CD69 Antigens