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Monolayer destruction by leukocytes from patients with multiple sclerosis
Abstract:
Separated lymphoid cells from patients suffering from multiple sclerosis (MS) were co-cultivated with various cell lines. Over 80% of such co-cultivations showed destruction of the tissue-culture monolayers, whereas less than 5% of "normal" blood co-cultivation behaved in the same manner. Because of the possible involvement of virus in the aetiology of MS, many positive co-cultivations were 1) examined electron-microscopically, but no virus particles were seen; and 2) tested for measles and herpes viruses using immunofluorescent techniques, but these also proved negative. Leukocytes from stroke patients showed monolayer destruction in about 50% of cases. Granulocyte contamination was high in the stroke blood samples. Reduction of granulocyte numbers to "normal" levels completely abrogated the effect in the stroke samples, but had no effect on the MS co-cultivations. Monolayer destruction by MS leukocytes also appeared not to be due to lymphotoxin.
Insights
Lymphoid cells from multiple sclerosis (MS) patients caused significant tissue-culture destruction, unlike normal cells. This effect in MS patients was not linked to common viruses or granulocytes, suggesting a unique cellular mechanism in MS pathogenesis.
Area of Science:
- Immunology
- Neuroscience
- Cell Biology
Background:
- Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system.
- The etiology of MS is not fully understood, with potential roles for viral infections and immune system dysregulation.
- Previous studies have suggested immune cell involvement in MS pathogenesis.
Purpose of the Study:
- To investigate the cytotoxic effects of lymphoid cells from MS patients on tissue-culture monolayers.
- To explore potential causative agents, such as viruses or specific cell types, contributing to this observed cytotoxicity in MS.
Main Methods:
- Co-cultivation of separated lymphoid cells from MS patients and healthy controls with various cell lines.
- Electron microscopy to detect viral particles in positive co-cultures.
- Immunofluorescent techniques to test for measles and herpes viruses.
- Comparative analysis with co-cultivations from stroke patients, including granulocyte manipulation.
Main Results:
- Over 80% of co-cultivations with MS lymphoid cells showed monolayer destruction, compared to less than 5% with normal cells.
- No viral particles were detected by electron microscopy, and measles/herpes viruses were negative via immunofluorescence.
- While stroke patient leukocytes caused destruction, this was abrogated by reducing granulocyte contamination, unlike the MS samples.
- The cytotoxic effect in MS was not attributed to lymphotoxin.
Conclusions:
- Lymphoid cells from MS patients possess a potent, intrinsic cytotoxic activity against tissue-culture cells.
- This MS-associated cytotoxicity is not mediated by common viral infections or granulocytes.
- The findings suggest a unique, non-viral, non-granulocyte-dependent mechanism contributing to MS pathogenesis.