Abstract
Tissue infiltrating lymphocytes were isolated from BALB/c line C4 preneoplastic hyperplastic alveolar nodules (HAN) and spontaneous tumours that arose from the HANs. NK activity of the lymphocytic infiltrates was tested in a 4 h chromium release assay using 51Cr labelled YAC cells. In situ lymphocytes of C4 HAN expressed 3-4 fold greater relative lytic activity (Pross et al., 1981) than did normal spleen cells whereas the relative lytic activity of C4 tumour infiltrates was equivalent or less than that of normal spleen cells. Spleen cells of all lesion bearers had reduced cytolytic capacity. YAC cell lysis by spleen cells and HAN infiltrates correlated with increasing E/T ratios. The degree of YAC lysis by C4 tumour infiltrates, however, either decreased, stayed the same, or increased non-exponentially with increasing E/T ratios especially at E/T greater than 50. Indeed, C4 tumour infiltrates from animals pretreated with anti-asialo GM1 (ASGM) could suppress the NK activity of normal spleen cells. The lytic activity of both C4 HAN and tumour infiltrates could be enhanced or depressed by in vivo treatment with poly IC or anti-ASGM, respectively. These results indicate that NK cells are activated or recruited into C4 preneoplastic lesions but their lytic activity wanes and suppressive activity arises with progression to neoplasia.
Highlights
Host infiltrates of C4 hyperplastic alveolar nodules (HAN) and C4 tumours isolated in elutriation fraction 2 (F2) contained 1-2 x 106 asialo GM 1 (ASGM) positive cells g- 1 tissue (Wei et al, 1986)
To further characterize these infiltrates, non-adherent F2 cells were stained with anti-ASGM or monoclonal anti-Mac 1 and analyzed by flow cytometry
Since we found previously that C4 tumour infiltrate preparations contained 30% or less tumour cell contamination, it was possible that C4 tumour cells competed with YAC cells for Natural killer (NK) effector cell binding sites
Summary
BALB/c mice originally obtained from the Cancer Research Laboratory, University of California, Berkeley, CA, were bred by brother-sister mating in our Animal Care Facility. Preneoplastic hyperplastic alveolar nodule (HAN) line C4, originally induced by dimethylbenzenthracene (Medina, 1976), was maintained in vivo by intra fat pad implantation into 3 week old female BALB/c mice. HAN tissue grows to fill the pads in 8-12 wks. The incidence of tumours arising spontaneously from the C4 HAN implants is 80%, with a latency period of around 6 months post HAN implantation. Normal mammary glands were from mid to late pregnant uniparous BALB/c female mice. YAC-1, a T cell lymphoma line induced by Moloney leukaemia virus in A/Sn mice, was maintained in RPMI 1640 containing 10% foetal calf serum (FCS), 2mM L-
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