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Lymphokine-activated killer (LAK) cells discriminate between Epstein-Barr virus (EBV)-positive Burkitt's lymphoma
Insights
Lymphokine-activated killer (LAK) cells generated with recombinant interleukin-2 (rIL-2) show differential lysis of Burkitt
Area of Science:
- Immunology
- Cell Biology
- Oncology
Background:
- Lymphokine-activated killer (LAK) cells are generated in vitro from mononuclear leukocytes stimulated with recombinant interleukin-2 (rIL-2).
- LAK cells possess cytotoxic activity against various tumor cells and virus-infected cells.
- Understanding LAK cell heterogeneity and target cell recognition is crucial for immunotherapy.
Purpose of the Study:
- To investigate the cytotoxic activity of in vitro generated LAK cells against different subtypes of Burkitt's lymphoma (BL) cell lines.
- To determine if LAK cells discriminate between BL cell lines based on phenotypic characteristics.
- To elucidate the cellular components and functional heterogeneity of LAK cell populations.
Main Methods:
- Generation of LAK cells from healthy donors using rIL-2.
- Analysis of LAK cell lytic properties using a 51Cr-release assay.
- Utilizing a target panel including Epstein-Barr virus (EBV)-positive BL cell lines (Raji, Group I/II, Group III) and EBV-transformed lymphoblastoid cell lines (LCLs), and K562 cells.
- Cell depletion and monoclonal antibody (MAb) studies to characterize effector cell subpopulations.
Main Results:
- LAK cells exhibited differential lysis of BL cell lines, strongly lysing Group I/II BL cells expressing common acute lymphoblastic leukemia antigen (CALLA) and BL-associated glycolipid antigen (BLA).
- Group III BL cells, lacking CALLA and BLA and exhibiting an LCL-like phenotype, were poorly lysed.
- Lymphoblastoid cell lines (LCLs) were generally resistant to lysis, while K562 cells were highly sensitive.
- Cell depletion and MAb studies indicated LAK cell heterogeneity, comprising at least two subpopulations: a tumor-specific component and a natural killer (NK)-cell-mediated component.
Conclusions:
- In vitro generated LAK cells demonstrate selective cytotoxicity against distinct BL cell subtypes.
- LAK cell-mediated lysis is influenced by the expression of specific surface markers (CALLA, BLA) on target tumor cells.
- LAK cell populations are functionally heterogeneous, containing both tumor-specific and NK-cell-mediated cytotoxic effector cells.
Abstract:
We have generated in vitro lymphokine-activated killer (LAK) cells from healthy donors by stimulating their mononuclear leukocytes with recombinant interleukin-2 (rIL-2) (100 U/ml). After 6 days in culture, the lytic properties of the LAK cells were analyzed in the 51Cr-release assay by utilizing a target panel of 6 paired lines consisting of an Epstein-Barr virus (EBV)-positive Burkitt's lymphoma (BL) cell line and an EBV-transformed lymphoblastoid cell line (LCL) from the same donor, the Raji BL line and the natural killer (NK) cell-sensitive K562 line. The patterns of lysis showed that the LAK cells discriminated between two categories of BL cell lines. Group I/II BL tumor cells which expressed the common acute lymphoblastic leukemia antigen (CALLA), the BL-associated glycolipid antigen (BLA) and phenotypically resembled biopsy cells were strongly lysed whereas group III BL cells which had assumed an LCL-like phenotype during culture and lacked the CALLA and BLA surface markers were only poorly lysed. The LCL targets were generally resistant to lysis but the K562 cell line was particularly sensitive. The outcome of cell depletion and monoclonal antibody (MAb) studies indicated that the LAK cell populations were phenotypically and functionally heterogeneous and consisted of at least 2 subpopulations of effector cells; a tumor-specific component and an NK-cell-mediated component.