Systemic and in-situ natural killer activity in tumour-bearing rats

Abstract

Summary.-Single-cell suspensions prepared by enzymatic disaggregation of an immunogenic 3-methylcholanthrene-induced sarcoma (Mc4OA) contain a significant proportion of infiltrating leucocytes (42%) comprising T lymphocytes, macrophages and non-phagocytic FcR+ lymphoid-like cells. Tumour-infiltrating lymphocytes (TIL) were isolated and purified by successive passage over Sephadex G-10 columns and their cytotoxic activity in vitro compared with that of lymphoid cells from normal rats and from tumour-bearers at different times after implantation. For this purpose, surviving target cells were quantified by incorporation of the y-emitting analogue of methionine,75Sel-methionine, in a 48-h assay which detected both cytotoxic and cytostatic effects. The reactivity of TIL, which was consistently demonstrable from 11 days after tumour transplantation, was essentially similar to that of normal splenic lymphocytes in magnitude and specificity. Reciprocal cytotoxicity tests using TIL and cultured targets from an antigenically unrelated tumour of similar aetiology (Mc57) showed that the manifestation of TIL cytotoxicity was determined, not by the tumour of origin, but by the susceptibility of the target cells. Evidence that the effector function of TIL was mediated in part by natural killer (NK) cells was derived from concurrent experiments using human myeloid cells (K562) as targets in an 18h 51Cr-release assay. In this system the level of NK activity was critically dependent on the numbers of tumour cells in the TIL population; contamination in excess of 2 % gave rise to dose -dependent inhibition of NK function. The results show that within a progressively growing tumour known to possess rejection antigens, NK reactivity was detected in the absence of a demonstrable tumour-specific cytotoxic component.

Natural killer cells in carcinomatous pleural effusions

“…Tumor cells contaminating tumor-infiltrating lymphocytes have been thought to account for the depression of NK activity in rat sarcoma [14]. The lack of NK activity of effusion lymphocytes could be attributed to contaminating tumor cells.…”

Natural Cellular Reactivities Mediated by Splenocytes From Mice Bearing Three Types of Primary Tumor

“…Moreover, we demonstrated that the inhibitor cells could be removed from splenocyte suspensions by passage through G-10 Sephadex columns. These Sephadex-adhering NK inhibitor cells could be either tumor cells (Moore and Moore, 1979), or macrophage-like cells (Padarathsingh et al, 1979). It is important to note that Sephadex-adhering cells constitute a majority, within the spleen of tumor bearers (60% or more) whereas only 10-20% of normal splenocytes express this charcteristic.…”

Human bronchoalveolar macrophage cytotoxicity for cultured human lung-tumour cells

“…Mononuclear leucocytes were recovered from the gradient interface and lymphocytes purified by passage down a Sephadex GIO column as described by . This procedure has been shown to enrich for a "natural killer" lymphocyte population in rodent tumours (Moore & Moore, 1979) and human peripheral blood (Mantovani et al, 1979). PMNL were recovered from the FT gradient pellet after removing the erythrocytes by sedimentation through a Dextran gradient (Boyiim, 1968 (1-3-42.3 x 106 total) as was the proportion of the major free lung cell types: BAM, lymphocytes and PMNL (Table).…”