Cell-Mediated Cytotoxicity, Allograft Rejection, and Tumor Immunity

Summary. Two transplantable, highly immunogenic syngeneic C57BL fibrosarcomas, FS1 and FS6, were shown to have tumour-specific rejection antigens, as shown by excision of the primary tumours and i.p. or i.m. injection of graded doses of the specific and unrelated tumour cells. I.p. challenge with tumour cells induced a large and relatively long-lasting increase in numbers of peritoneal leucocytes. Macrophage monolayers prepared from such exudates were, in general, non-specifically cytotoxic, though occasional specific cytotoxicity was detected. T lymphocytes isolated from exudates were shown to kill in a specific manner. When immunized mice were challenged with the specific tumour cells to elicit large numbers of peritoneal cytotoxic cells, and with graded doses of the non-cross-reacting tumour cells at the same time or at various times thereafter, growth of the non-related tumours occurred in all cases and only the specific tumour was rejected. Moreover, Winn tests, in which the inflammatory cells were mixed with unrelated tumour cells and implanted i.m., did not delay tumour growth. The relevance of these findings to the role of macrophages and lymphocytes in syngeneic tumour rejection is discussed.

mentioning

confidence: 99%

Lack of correlation between in vivo rejection of syngeneic fibrosarcomas and in vitro non-specific macrophage cytotoxicity

Evans¹,

Booth²,

Spencer³

1978

“…of approximately 70,000. It prevented the growth of a fibrosarcoma in mice.CELL killing by lymphoid cell lines, either mediated by antibody or by direct cell-to-cell contact (K-cells and T-cells), is well documented (reviewed by Cerottini and Brunner, 1974 Heparinized blood was left at room temperature for 2 h: the buffy coat was then taken off and spun at 500 g for 10 min at 50C.The WBC were re-suspended in RPMI-1640 culture medium supplemented with antibiotics (100 iu/ml penicillin; 100 ,ug/ml streptomycin) and foetal bovine serum at a final concentration of 10%. The cells were then seeded in 125-ml Erlenmeyer's flasks with 50 ml of culture medium, and placed in a humidified CO2 incubator in an atmosphere of 5% C02 95°% air at 370C.…”

mentioning

confidence: 99%

“…CELL killing by lymphoid cell lines, either mediated by antibody or by direct cell-to-cell contact (K-cells and T-cells), is well documented (reviewed by Cerottini and Brunner, 1974 Heparinized blood was left at room temperature for 2 h: the buffy coat was then taken off and spun at 500 g for 10 min at 50C.…”

mentioning

confidence: 99%

A human haemic cell line capable of cellular and humoral killing of normal and malignant cells

Karpas¹

1977

Summary.-A line of human leukaemia-derived cells is described that kills a wide range of human and animal cell lines, whether normal or malignant, even at a ratio of 1: 1. During exposure to the target cells, the killer cells released a factor into the culture medium which destroyed target cells in the absence of the killer cells. This phenomenon occurs without exogenous complement and requires no pre-treatment of target or killer cells. The humoral factor is a protein precipitable by 60% saturation of ammonium sulphate and has a mol. wt. of approximately 70,000. It prevented the growth of a fibrosarcoma in mice.CELL killing by lymphoid cell lines, either mediated by antibody or by direct cell-to-cell contact (K-cells and T-cells), is well documented (reviewed by Cerottini and Brunner, 1974 Heparinized blood was left at room temperature for 2 h: the buffy coat was then taken off and spun at 500 g for 10 min at 50C.The WBC were re-suspended in RPMI-1640 culture medium supplemented with antibiotics (100 iu/ml penicillin; 100 ,ug/ml streptomycin) and foetal bovine serum at a final concentration of 10%. The cells were then seeded in 125-ml Erlenmeyer's flasks with 50 ml of culture medium, and placed in a humidified CO2 incubator in an atmosphere of 5% C02 95°% air at 370C. The medium was changed every 5 days by aspirating about half the medium and replacing it with fresh medium. For large-scale growth, the cells were transferred into waterjacketed spinner cultures (Wingent Ltd., Cambridge) of 1-5 litres' capacity. To test the cytotoxic action of the cultured cells, they were counted, separated from the growth medium and re-suspended in fresh RPMI-1640 with or without serum to give the desired concentration, before being added to cultures of target cells.Morphological and immunological propertie8.-For morphological studies cytocentrifuged smears of the cultured cells were stained

“…Specific cellular lysis of tumour cell is mainly performed by the classic T-cell immunity mechanism (Cerottini & Brunner, 1974) or the interaction of antibody with normal lymphoid cells, the latter being referred to as antibody-dependent cellular cytotoxicity (ADCC). The precise mechanism of ADCC is not understood, though it is known that the specificity of this imimunological reaction is determined by antibody bound to membrane-associated (Lamon et al, 1976;Shore et al, 1976a) and also against Durantez & Zighelboim, 1976), histocompatibility (Yust et al, 1974; A@~~~s s , Jeannet & Vassalli, 1976) or auto-antigens (Feldmann et al, 1976).…”

Section: Discussionmentioning

confidence: 99%

Antibody-dependent cellular cytotoxicity against drug-induced antigens in L5178Y mouse lymphoma

Franco¹,

Veronese²,

Lévi³

et al. 1982

In vivo treatment with antineoplastic compounds has been reported to lead to the expression of new antigenic specificities which were not detected on parental cells, and which were transmissible as a genetic character. The current study is concerned with antibody-dependent cellular cytotoxic (ADCC) activity in serum of syngeneic mice challenged with LY/DTIC cells, a subline of LY murine lymphoma, antigenically altered by the drug DTIC. LY/DTIC target cells coated with LY/DTIC-immune serum were specifically lysed by virgin lymphocytes. The genetic background of the effector cells, whether syngeneic, allogeneic or xenogeneic, did not produce significant differences in the percentage of target-cell lysis. ADCC activity was reduced when the immune serum was added directly to the incubation medium, without precoating. Although sera from individual animals exhibited different levels of ADCC activity, they nevertheless followed the general trend of the pooled sera. Peak activity of ADCC was obtained in the sera collected on Days 8 and 30 after LY/DTIC cell challenge. The ADCC activity elicited by LY/DTIC cells may contribute to the rejection of drug-altered tumour cells.