This study examined the heterogeneity of lymphokine-activated killer (LAK) cells in terms of phenotype of precursors and effectors, generation pathways, and cellular, lymphokine, phar- macological regulators involved in endogenous and exogenous pathways. The serological phenotype of precursors and effectors of LAK cells against different target cells was not the same: LAK cells against HFL/b(H-2b) could be derived from Thyl, CD4, CD4 CD8, and AsGMl' cells, whereas precursor of LAK cells against P815 cells(H-2d) could be Thyl+, CD4, CD8+, and AsGM1+ cells. Effectors of LAK cells against HFL/b were Thy1+, CD8- cells but LAK cells against P815 were Thy1+, CD8 cells. LAK cells were generated in different pathways: (a) the endogenous pathway in which LAK cells were generated by culturing splenocytes with syngeneic peritoneal macrophages and indomethacin, and (h) the exogenous pathway in which LAK cells were generated by culturing splenocytes with exogenous interleukin-2(IL-2). Depletion of Thy1+, CD4+, AsGM1+ cells from splenocytes suppressed endogenous LAK cell generation, whereas depletion of Thyl+, AsGM1+ cells, not CD4+ cells, suppressed exogenous LAK cell generation against HFL/b. IA+ macrophages and CD4+ T cells were the ancillary cells that were responsible for producing lymphokines in endogenous pathways. Regarding cytokine requirement, interleukin-4 (IL-4) synergized with IL-2 to induce LAK cells both in endogenous and exogenous pathways. Interferon a, B(lIFN a, B) had no effect both in endogenous and exogenous pathways. Interferon r(IFN r) and prostaglandin E2(PGE2) suppressed endogenous LAK cell generation but had no effect in exogenous pathway. Our study demonstrated that LAK cells are heterogeneous both in precursors and effectors, and different cellular, lymphokine, pharmacological regulators might be involved in the generation of efficient LAK cells in endogenous and exogenous pathways.
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