Anti-idiotypic T-cell activation in multiple myeloma induced by M-component fragments presented by dendritic cells.
The monoclonal immunoglobulin (Ig) (M-component) secreted by the tumour plasma cells in multiple myeloma (MM) has specific antigenic determinants (idiotypes; id) that can serve as tumour-specific antigens. The intact Ig molecule is a weak antigen, and small fragments of id protein might be more immunogenic for the induction of id-specific immunity. Dendritic cells (DC) have attracted attention as the most efficient antigen-presenting cells and promising adjuvants for immunotherapy in tumours. In this study the in vitro T-cell response against F(ab')2 and Fab fragments, heavy and light chains of the M-component was examined in five patients with MM clinical stage I. All fragments were able to stimulate T cells but F(ab')2 or Fab fragments and heavy chains induced a stronger response than light chains. DC induced a significantly stronger id-specific immune response than monocytes. Moreover, with DC as antigen-presenting cells, a predominant interferon (IFN)-gamma (type-1 T-cell) response was seen in all patients. Both IFN-gamma and interleukin (IL)-4 (type-1 and type-2 T-cell) responses were noted when monocytes were used. Our study suggests that DC pulsed with idiotypic fragments such as F(ab')2 fragment and heavy chain can be used for the induction of type-1 anti-idiotypic T-cell response for immunotherapy in MM.
Dabadghao
S
S
Centre for Molecular Medicine, Department of Medicine, Karolinska Hospital, Stockholm, Sweden.
Bergenbrant
S
S
Anton
D
D
He
W
W
Holm
G
G
Yi
Q
Q
D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007124:Immunoenzyme Techniques; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology*; D051798:Inhibitor of Differentiation Protein 1; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D009101:Multiple Myeloma / Q000276:immunology* / Q000473:pathology; D012097:Repressor Proteins; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D014157:Transcription Factors / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; C497453:ID1 protein, human; D007140:Immunoglobulin Fab Fragments; D007075:Immunoglobulin M; D051798:Inhibitor of Differentiation Protein 1; D012097:Repressor Proteins; D014157:Transcription Factors; D015847:Interleukin-4; D007371:Interferon-gamma