Conjugate formation between effector and target as a function of cytotoxicity in antibody-dependent killing of AK-5 tumor.

The present study was carried out to mechanistically view a possible correlation between the process of, conjugate formation and its relation to target cell death. AK-5 killing is mediated by CD8+ natural killer cells through ADCC. Immune effectors on exposure to antibody primed AK-5 tumor cells formed tight conjugates. Ability of various cell types (NK, T, monocytes and macrophages) to form conjugates was evaluated. Marked increase in the number of NK cells binding to the target as compared to the other cell types was observed. Cytotoxicity of free and bound effectors against antibody tagged AK-5 cells demonstrated a reduced cytotoxic ability of the former in contrast to a significantly high lytic potential of the bound effectors. The results highlight the requirement for priming of NK cells which mediate killing of AK-5 tumor and provide additional evidence that formation of stable conjugates acts as the first signal for triggering lymphocyte activation and effective target cell lysis.

Heterogeneity in DNA content & proliferative status of human brain tumours.

Intra-tumour and inter-tumour heterogeneity in the cytokinetic organization was studied in 235 primary human brain tumours. DNA index (DI; relative tumour cell DNA content) and proliferating fraction (%PF; a measure of proliferative status) were analyzed in tumour biopsy by flow cytometry using a DNA specific fluorochrome (DAPI) and internal standards (chicken erythrocytes, CE). Incidence of micronuclei was studied in tumour biopsy tissue as well as in explants maintained in organ culture. Clonal diversity (implied by the presence of multiple peaks in the DNA histograms) was highest among medulloblastomas (44%) followed by gliomas (19%) and meningiomas (14%). Nearly 85 per cent of the malignant gliomas analyzed (histological grade III/IV) exhibited a great deal of regional variation in the proliferative status as well as micronuclei frequency as compared to meningiomas. Inter-tumoural variations in the DNA content was highest among gliomas (0.9 < DI < 3.6) and lowest among schwannomas (1.7 < DI < 2.2). Similarly, the distribution of %PF values was also broader (10-49%) in gliomas as compared to the other primary brain tumours (5-36%). Analysis of tumours taking both DI and %PF values improved the ability to discern histologically graded low and high tumours. Analysis of clonal diversity and spatial heterogeneity in the cytokinetic parameters could complement the clinicopathological findings in assessing the biological behaviour of human brain tumours, facilitating the prognostification and design of otpimal treatment regimen.

Status of different immune cells during regression of a rat histiocytoma.

Status of CD4 and CD8 positive T-lymphocytes, natural killer cells and macrophages has been studied in animals which reject AK-5 histiocytoma. Analysis of immune cells which enter the tumour showed higher number of CD8 positive and NK cells around day 25 after tumour transplantation, suggesting their participation in tumour rejection.