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Lymphokine-activated killer (LAK) and adherent LAK (A-LAK) activity in multiple sclerosis
J Satoh1, S U Kim, L F Kastrukoff
1Department of Medicine, University Hospital, University of British Columbia, Vancouver, Canada.
Insights
Lymphokine-activated killer (LAK) cells showed low cytotoxicity against oligodendrocytes (OL), with no difference between multiple sclerosis (MS) patients and controls. Adherent LAK cells demonstrated higher cytotoxicity against OL. Keywords: LAK cells, oligodendrocytes, multiple sclerosis, cytotoxicity.
Area of Science:
- Immunology
- Neuroscience
- Cell Biology
Background:
- Multiple sclerosis (MS) is a demyelinating disease affecting the central nervous system.
- Oligodendrocytes (OL) are crucial glial cells responsible for myelin production in the CNS.
- The role of immune cells, such as lymphokine-activated killer (LAK) cells, in OL damage is not fully understood.
Purpose of the Study:
- To investigate the cytotoxic activity of human LAK cells against oligodendrocytes (OL) in the context of multiple sclerosis (MS).
- To compare the cytotoxic potential of unfractionated LAK cells and enriched adherent LAK (A-LAK) cells against OL.
- To determine if LAK cell activity against OL differs between MS patients and healthy controls.
Main Methods:
- Human LAK cells were generated from macrophage-depleted peripheral blood mononuclear cells (PBMC) and cultured with recombinant human interleukin-2 (IL-2).
- Cytotoxicity assays were performed using primary cultures of bovine OL and tumor cell lines (Raji cells).
- Flow cytometry was used to characterize A-LAK effector cells (CD4-, CD8+, CD16+).
Main Results:
- LAK cells exhibited high cytotoxicity against Raji cells but low cytotoxicity against bovine OL.
- IL-2 concentration did not significantly enhance LAK cell cytotoxicity against OL.
- No statistically significant differences in LAK cell activity against OL were found between MS and control groups.
- A-LAK cells demonstrated enhanced cytotoxicity against both bovine OL and tumor cell lines compared to unfractionated LAK cells.
- A-LAK cells mediated lysis of OL from various animal species.
Conclusions:
- LAK and A-LAK cells can induce cytolysis of OL in vitro, similar to their effect on tumor cells.
- The study did not find significant differences in LAK cell-mediated OL lysis between MS and control groups.
- A-LAK cells, characterized as CD4-, CD8+, CD16+, show a greater cytotoxic potential against OL.
Abstract:
The cytotoxic activity of lymphokine-activated killer (LAK) cells against enriched cultures of oligodendrocytes (OL) was investigated in multiple sclerosis (MS) and controls. Human LAK cells, derived from macrophage-depleted peripheral blood mononuclear cells (PBMC) and incubated with recombinant human interleukin-2 (IL-2) (20-80 U/ml), mediated high levels of cytotoxicity against Raji cells but low levels of cytotoxicity against primary cultures of bovine OL. Cytotoxicity was not enhanced by incubation with a high level of IL-2 (500 U/ml). No statistically significant differences in LAK cell activity against bovine OL were observed among the study groups. Enriched adherent LAK (A-LAK) cells mediated greater levels of cytotoxicity against both bovine OL and tumor cell lines than unfractionated LAK cells. Flow cytometric analysis indicated that A-LAK effector cells were CD4-, CD8+, and CD16+. Furthermore, A-LAK cells mediated lysis of OL derived from several different animal species. Our results suggest that LAK and A-LAK cells can mediate cytolysis of OL in culture similar to that observed with a number of different tumor cell lines. However, no significant difference in cytolysis was identified between MS and control groups in this study.
