Natural cytotoxicity to autologous antigen-pulsed dendritic cells in multiple myeloma.
To analyse autologous lymphocyte cytolytic activities of potential importance for cell-based immunotherapy in multiple myeloma (MM), in vitro differentiated dendritic cells (DCs) loaded with patient-specific monoclonal immunoglobulin (mIg) were used as autologous target cellsin cytotoxicity assays. Effector populations consisted of purified natural killer (NK) cells (CD56+, CD3-) and T cells (CD3+). The MM patients' NK cells cultured in the presence of interleukin 2 (IL-2) showed pronounced cytotoxic activity towards autologous mature DCs. Autologous MM DC targets displayed similar susceptibility to NK cell lysis, compared with allogeneic control DC targets, despite high surface expression of self major histocompatibility complex (MHC) antigens. However, some degree of classic MHC class I-mediated negative regulation was implicated in the NK-DC interactions, as indicated by class I blocking experiments. NK-mediated lysis was also discerned towards primary autologous MM cells. The results indicated that the major effector mechanism was mediated through the perforin-granzyme exocytosis pathway. In conclusion, NK cells from MM patients displayed significant and consistent cytotoxicity towards autologous mature DCs, suggesting that innate immunity could be implicated in MM and may influence the outcome of the administration of tumour antigen-pulsed DCs in treatment trials.
Division of Hematology, Centre for Molecular Medicine, Karolinska Institutet and Hospital, Stockholm, Sweden.
Chengyun
C
Zheng
Masih
M
Ostad
Margareta
M
Andersson
Fredrik
F
Celsing
Göran
G
Holm
Anne
A
Sundblad
D002118:Calcium / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007376:Interleukin-2 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D009101:Multiple Myeloma / Q000276:immunology*; D014407:Tumor Cells, Cultured
D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; D002118:Calcium