Spontaneous human lymphocyte-mediated cytotoxicity against tumor target cells

Pross, Hugh F.; Baines, Malcolm G.

doi:10.1007/bf00200062

Cited by 129 publications

(16 citation statements)

References 75 publications

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“…Lymphocytes derived from blood or spleen of many animal species and human donors have been shown to have spontaneous cytotoxic activity against many types of tumor cell lines in the absence of any previous sensitization procedure (Herberman and Holden, 1978;Pross and Baines, 1977). Cells responsible for this cytotoxicity have been termed natural killer (NK) cells and are generally believed to be different from T cells, B cells and macrophages (Herbermann and Holden, 1978;Pross and Baines, 1977). Some investigators, however, have demonstrated sheep erythrocyte receptors on human NK cells, which is a characteristic usually associated with T cells (West et al, 1977).…”

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confidence: 99%

Regulation of natural killer activity in vivo. II. The effect of alcohol consumption on human peripheral blood natural killer activity

Saxena

Mezey

Adler

1980

Intl Journal of Cancer

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Natural killer (NK) activity of human peripheral blood lymphocytes (HPBL) was studied in 32 alcoholics and 15 control subjects in a 4-h chromium release assay using K562 tumor target cells. The natural killer activity of human peripheral blood lymphocytes in alcoholics was significantly higher than the level found in the control group. NK activity of PBL from alcoholics was still higher than that of similarly treated PBL from control subjects after carbonyl iron and magnet treatment, or after passage through a nylon wool column or after removal of cells rosetting with sheep erythrocytes. Changes in T cell, B cell or macrophage populations, therefore, are not the mechanism for increased NK activity in alcoholics.

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Regulation of natural killer activity in vivo. II. The effect of alcohol consumption on human peripheral blood natural killer activity

Saxena

Mezey

Adler

1980

Intl Journal of Cancer

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“…Human blood lymphocytes have a lytic effect in vitro against certain tumor cell lines (1). The active population is heterogeneous with regard to its cell surface characteristics (2-7).…”

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Target selectivity of interferon-induced human killer lymphocytes related to their Fc receptor expression.

Masucci¹,

Masucci²,

Klein³

et al. 1980

Proc. Natl. Acad. Sci. U.S.A.

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Human blood lymphocytes were fractionated on the basis of surface characteristics such as adherence to nylon wool and expression of erythrocyte (E) and Fc receptors. The various subsets were incubated with interferon for 3 hr. Two cell lines that differ in sensitivity to the natural killer effect, K562 and Daudi, were exposed to these lymphocytes (i.e., their sensitivity to interferon-activated killing was tested). Cell line Daudi, with a low sensitivity to the natural killer effect, was also affected by interferon-activated killing. The efficiency of the nonadherent subsets, separated accor in to the expression of E receptor, ranked similarly in natural killing (anti-K562) and interferon-activated killing (anti-K562 and anti-Daudi) in the following order: E receptor-negative cells, low-affinity E receptor-positive cells, and high-affinity E receptor-positive cells.Further separation on the basis of Fc receptor expression revealed a difference between the two targets. The Fc receptorpositive and -negative cells that did not express high-affinity E receptors killed K562 with similar efficiency whereas Daudi cells were more sensitive to the effect of cells devoid of Fc receptor. Results obtained with other targets suggested that T cell lines behave similarly to K562 and that the difference may be generally valid for T and B cell lines.

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“…Apart from technical reasons, the conflicting findings made by different workers have their basis in the fact that any disease-related cytotoxicity, if it exists at all in a given system, will be masked to different degrees by what is now commonly called "natural lymphocyte-mediated cytotoxicity". Natural cytotoxicity, usually selective for a variety of target cells, is displayed by lymphocytes from patients and healthy donors alike and without any obvious relation to disease or known events of preceding sensitization (Pross and Baines, 1977;Herberman and Holden, 1978; Moller, 1979). Natural cytotoxicity is by itself a heterogenous phenomenon, involving both an innate, genetically determined reactivity with no apparent immunological basis (Kiessling and Haller, 1978) and a reactivity where cytotoxicity is the expression of a variety of conventional antigen recognition phenomena (Perlmann and Cerottini, 1979).…”

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confidence: 99%

Cytotoxicity in vitro of blood lymphocytes from bladder cancer patients and controls to allogeneic or autologous tumor cells derived from established cell lines or short‐term cultures

Troye

Vilien²,

Pape³

et al. 1980

Intl Journal of Cancer

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Blood lymphocytes from small groups of patients with transitional-cell carcinoma of the urinary bladder (TCC), clinical controls (CC) or healthy donors (HD) were tested for cytotoxicity in vitro by a 51Cr-release assay. The target cells were either from TCC or control tissue (long-term cultures) or were from short-term TCC cultures, kept in vitro for 10-20 transfer generations. When tested with allogeneic target cells from long-term cultures, TCC patients' lymphocytes tended to be more cytotoxic to TCC targets than to control targets. For the control lymphocytes this was not seen. A large proportion but not all of the cytotoxicity to these target cells was due to immunoglobulin-dependent cellular reactions, probably mediated by natural and disease-related antibodies of the lymphocyte donors, since it was significantly inhibited by Fab-fragments of rabbit antibodies to human immunoglobulin. Moreover, it was, to a large extent, mediated by lymphocytes with Fc-receptors for IgG. For seven of the TCC target cell cultures (two long-term and five short-term) autologous lymphocytes were also available for testing. While two patients were non-reactive to their own tumor cells, five reacted strongly in the autologous combinations. These autologous reactions were immunoglobulin-independent and were mediated by Fc-receptor-negative effector cells. In some instances, autologous cytotoxicity was accompanied by similar reactions to some of the allogeneic TCC targets but not to the allogeneic non-TCC control targets. On the basis of available information on HLA antigens in this material, the pattern of cross-reactions suggests that the cytotoxicity encountered in the autologous and in some of the allogeneic TCC-combinations may be the expression of antibody-independnet but specific CTL-mediated reactions, regulated by HLA. However, at the present stage of the investigation, other mechanisms must also be considered since the target cells from short-term TCC cultures were sometimes lysed by control lymphocytes in immunoglobulin-independent reactions. Whatever the explanation, the results show that the cytotoxicity observed in the in vitro systems is usually the net result of several different types of reaction. Which effector cell types and which mechanism of recognition will predominate in a given lymphocyte/target cell combination is greatly influenced by the nature and origin of the target cells used.

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Spontaneous human lymphocyte-mediated cytotoxicity against tumor target cells

Cited by 129 publications

References 75 publications

Regulation of natural killer activity in vivo. II. The effect of alcohol consumption on human peripheral blood natural killer activity

Regulation of natural killer activity in vivo. II. The effect of alcohol consumption on human peripheral blood natural killer activity

Target selectivity of interferon-induced human killer lymphocytes related to their Fc receptor expression.

Cytotoxicity in vitro of blood lymphocytes from bladder cancer patients and controls to allogeneic or autologous tumor cells derived from established cell lines or short‐term cultures

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