Characteristics Of Natural Killer Cells Research Articles

In vivo anti-tumor effects of local adoptive transfer of mouse and human cultured lymphoid cells.

Mouse and human lymphoid cells were cultivated in the presence of T-cell growth factor (TCGF) and evaluated for their in vivo anti-tumor effect in mice. Cultured spleen cells of normal BALB/c mice or of mice bearing the M109 tumor had a high level of cytotoxic activity in vitro against a variety of tumor target cells and had characteristics of natural killer cells. These cultured cells were evaluated for their in vivo cytotoxic activity by a mixture with [125I]dUrd-labelled M109 tumor cells (2 x 10(5)) at a 30:1 ratio and inoculation of the mixture into the footpads of BALB/c mice. The level of radioactivity remaining in the footpad was determined at various periods following inoculation of radiolabelled tumor cells. The presence of cultured cells in the inocula caused a marked decrease in the footpad radioactivity by 24 h. However, the slope of clearance of the radiolabel then became similar to that in the control mice. The cultured cells delayed, but did not prevent, tumor appearance, and did not influence the subsequent rate of growth of the tumors. The transient effects of the cultured cells contrasted with the more prolonged in vivo effects of alloimmune lymphocytes, and this may be due to their short survival period. Ninety-nine percent of [125I]dUrd-labelled cultured mouse lymphoid cells were eliminated within 48 h of i.f.p. inoculation. Cultured human lymphoid cells, initiated from the blood of normal donors, also had a high level of cytotoxic activity in vitro and were evaluated for their in vivo effects by intra-footpad inoculation into nude mice, together with radiolabelled human tumor cell lines, G-11 or HT-29. In vivo cytotoxic activity of the human cultured lymphoid cells correlated with their cytotoxic effect in vitro. These results indicate that cultured mouse an human effector cells have appreciable in vivo cytotoxic effects against tumor cell lines. However, the transient duration of these effects may limit their immunotherapeutic potential.

Cytotoxic effector cells with the characteristics of natural killer cells in the lungs of mice

Cells with in vitro cytotoxicity against tumor targets in a short-term 51Cr release assay have been recovered from the lungs of mice that were either untreated or injected with biological or synthetic agents 1--3 days earlier. The cytotoxic effector cells were non-adherent, non-phagocytgic and shared many characteristics with splenic natural killer (NK) cells. This finding is discussed with particular regard to our previous observations on the rapid in vivo elimination from the lungs of intravenously injected, radiolabelled tumor cells.

Promonocytes Have the Functional Characteristics of Natural Killer Cells

Promonocytes isolated from a 5-day-old L-fibroblast-conditioned liquid bone marrow culture show strong NK cell cytotoxicity. They kill YAC target cells in a short-term 125IUDR-release assay whereas P815 targets are unaffected. This NK-like cytotoxicity is enhanced in the presence of interferon preparations. Morphologically, these promonocytes resemble a medium size lymphocyte with a high nucleus to cytoplasma ratio, they are nonadherent, nonphagocytic, and negative in nonspecific esterase staining. Promonocytes are precursor cells from macrophages, which have not yet developed the typical macrophage criteria. Within 24 to 48 hr they mature to adherent macrophages. We have shown previously, that the same promonocytes have the capacity to perform K cell killing of antibody-coated tumor target cells. The cytotoxic effector functions of promonocytes are abolished when the cells are treated with the alloantimacrophage serum Mphi 1.2 plus rabbit C. The relationship or similarity between K cells, NK cells and promonocytes is discussed.

Corynebacterium parvum-induced peritoneal exudate cells with rapid cytolytic activity against tumour cells are non-phagocytic cells with characteristics of natural killer cells.

Peritoneal exudate cells taken from mice 3 days after intraperitoneal treatment with Corynebacterium parvum (Cp) have been shown to kill specifically certain tumour targets in vitro. We have analysed in detail such Cp-induced cytotoxic cells as to their cellular characteristics, considering the fact that size and charge characteristics of cellular subgroups are useful markers in describing their representative characteristics. We could thus show that the cytolytic cell could not be classified as a macrophage. They behaved, in every manner analysed, exactly as the previously defined natural killer cells found in the lymphoid organs of normal mice.