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Analysis on functional heterogeneity of lymphokine activated killer lak cells and tumor infiltrating lymphocytes til at the clonal level



Analysis on functional heterogeneity of lymphokine activated killer lak cells and tumor infiltrating lymphocytes til at the clonal level



Sapporo Medical Journal 60(2): 205-214



We have analyzed interleukin-2 stimulated killer activity derived from peripheral blood lymphocytes (PBL) and tumor infiltrating lymphocytes (TIL) at the clonal level by a limiting dilution technique. The number of obtained clones from LaK and TIL were 34 and 78, respectively. The killer activity of these clones was examined against autologous tumor cells and Daudi cells as targets. About half of the PBL and TIL clones showed significant cytotoxicity against autologous tumor and/or Daudi cells. It was noteworthy that the specific cytotoxicity against autologous tumor cells (CTL-Like activity) was observed in 9 of 14 LAK killer clones and in 30 of 41 TIL killer clones. Surface marker analysis indicated that all the CTL-like clones were either CD3+4+8- or CD3+4-8+, and there was no significant difference in cytotoxicity between them. On the other hand, about half of the LAK and TIL clones had no cytotoxic effect against Daudi and/or autologous tumor cells. On the CTL induction system, these non-killer clones also showed regulatory functions, such as augmentation and suppression. These results suggest that IL-2 activated cells, both from peripheral blood and tumor tissue have not only a direct cytotoxic activity, but also an indirect helper function which was mediated by regulatory T cell.

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