Dendritic cells loaded with apoptotic tumour cells induce a stronger T-cell response than dendritic cell-tumour hybrids in B-CLL.
Dendritic cells (DC) are professional (specialised) antigen-presenting cells that can capture antigen from apoptotic tumour cells and induce MHC class I- and II-restricted responses. Also, DC fused with tumour cells may be effective for immune response induction. Both cell preparations may be considered as vaccine candidates in a therapeutic approach. We examined autologous T-cell activation by DC that had endocytosed leukaemic B-cell apoptotic bodies (Apo-DC) and compared it to the T-cell stimulatory capacity of DC that were fused with tumour cells. Following incubation, 22.6+/-6.2 (mean+/-s.e.m.) of DC had endocytosed leukaemic cells, while the frequency of DC-leukaemic cell hybrids was 10.5+/-2.6%. Apo-DC and hybrid cells both demonstrated the ability to stimulate a tumour-specific T-cell immune response in vitro. A T-cell proliferation response was also observed in four out of five CLL patients when using Apo-DC. However, fusion hybrids lacked the ability to elicit a proliferative response. Apo-DC also induced an IFN-gamma response, as did hybrid cells. The cytokine response induced by Apo-DC was significantly higher than that induced by fusion (P<0.05). This study shows that endocytosed apoptotic tumour cells induced a significantly stronger T-cell response than DC hybrids; and as such should be a better candidate for vaccine production.
Immune and Gene Therapy Laboratory, CCK, Karolinska Hospital, Stockholm, Sweden.
P
P
Kokhaei
M R
MR
Rezvany
L
L
Virving
A
A
Choudhury
H
H
Rabbani
A
A
Osterborg
H
H
Mellstedt
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017951:Antigen Presentation; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D002455:Cell Division; D002459:Cell Fusion; D002678:Chimera; D003713:Dendritic Cells / Q000276:immunology*; D004705:Endocytosis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D007167:Immunotherapy; D007371:Interferon-gamma / Q000378:metabolism; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000628:therapy; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma