Enhancement of anti-tumor activity of natural killer cells by BALL-1, a B cell lymphoma line.
The anti-tumor activity of human peripheral blood mononuclear cells (PBMC) against various tumor cell line cells (K562, Daudi, KMG-2, and KATOIII) was enhanced by coculture with irradiated BALL-1, but not with other irradiated B cell line cells (NALM-1, Namalwa, and Daudi). PBMC cocultured with BALL-1, however, failed to exhibit evident cytotoxicity against autologous concanavalin A-induced lymphoblasts. The enhancement of the anti-tumor activity seemed not to be correlated with EBNA and HLA-DR expression on B cell line cells. Monoclonal antibodies (mAbs) against interleukin (IL)-2, interferon-gamma, IL-12, IL-15, tumor necrosis factor-alpha and lymphotoxin showed little or no suppression of the anti-tumor activity of PBMC treated with irradiated BALL-1. Furthermore, the culture supernatants of BALL-1 failed to enhance the anti-tumor activity of PBMC, suggesting no involvement of soluble factors in the induction of the anti-tumor activity. The anti-tumor activity of PBMC treated with BALL-1 was synergistically enhanced by an additional IL-2 stimulation. Periodate-lysine-paraformaldehyde-fixed, but not ethanol- or acetone-fixed, BALL-1 could significantly enhance the anti-tumor activity. Furthermore, BALL-1-derived membrane fraction, but not that of Daudi, enhances the anti-tumor activity. It was thus suggested that some membrane glycoproteins on the cell surface of BALL-1 play a crucial role in the induction of the anti-tumor activity. By analysis using mAbs against human leukocytes, we found that depletion of CD11b, CD16, and CD56-positive cells resulted in decreased anti-tumor activity, suggesting that the main effector cells in the BALL-1-induced anti-tumor activity were natural killer (NK) cells. The present results thus raise the possibility that BALL-1, probably via membrane glycoproteins, modulates NK cell-mediated anti-tumor activity.
Hirashima
M
M
Department of Immunology and Immunopathology, Kagawa Medical School.
Yoshida
N
N
Seki
M
M
Okada
H
H
Takamura
S
S
Mihara
Y
Y
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018920:Coculture Techniques; D003208:Concanavalin A / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007155:Immunologic Factors; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000502:physiology*; D016131:Lymphocyte Subsets; D008214:Lymphocytes / Q000187:drug effects; D016393:Lymphoma, B-Cell / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology*; D016707:Tissue Fixation; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D007155:Immunologic Factors; D007376:Interleukin-2; D003208:Concanavalin A; D007371:Interferon-gamma