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High effector-memory CD8+ T-cell levels correlate with high PML risk in natalizumab-treated patients
Asma Beldi-Ferchiou1, Abir Wahab2, Matthieu Duchmann3
1Asma Beldi-Ferchiou and Valérie Molinier-Frenkel, AP-HP, Henri Mondor University Hospital, Department of Biological Hematology and Immunology, Université Paris Est Créteil, I-BIOT, F-94010 Creteil, France.
Background:
Progressive multifocal leukoencephalopathy (PML) is a severe complication of natalizumab (NTZ) treatment in multiple sclerosis (MS) patients. Based on the analysis of cryopreserved cells, several reports have showed that CD62L+ CD4+ T-cells percentage drops before PML onset.
Objective:
To analyze CD62L and CD45RA expression on fresh-blood CD4+ and CD8+ T-cells from NTZ-treated patients, according to their estimated PML risk.
Methods:
We prospectively enrolled 74 MS patients, including 62 NTZ-treated, and stratified them into low, intermediate and high PML risk groups. Circulating naïve and memory T-cell subsets were analyzed by flow cytometry.
Results:
We found no correlation between the percentage of CD62L+ CD4+ T-cells and PML risk. In contrast, the repartition of CD8+ T-cells subpopulations was altered in the high risk group: both the percentage and absolute count of CD8+ CD62L- CD45RA- effector memory T- cells (TEM) was significantly higher compared to patients at lower risk despite similar CD3+ and CD8+ T-cell counts. One high-risk patient with elevated CD8+ TEM and CD62L+ CD4+ T-cell levels developed PML six months after sampling.
Conclusion:
Our results suggest that CD8+ TEM cells should be evaluated in larger studies as a potential surrogate marker of PML risk in NTZ-treated patients.
Insights
Progressive multifocal leukoencephalopathy (PML) risk in multiple sclerosis (MS) patients treated with natalizumab (NTZ) may be linked to CD8+ effector memory T-cells (TEM). Elevated CD8+ TEM cells, not CD4+ T-cells, indicate higher PML risk.
Area of Science:
- Immunology
- Neurology
- Pharmacology
Background:
- Progressive multifocal leukoencephalopathy (PML) is a serious complication of natalizumab (NTZ) therapy in multiple sclerosis (MS) patients.
- Previous studies indicated a drop in CD62L+ CD4+ T-cells before PML onset, based on cryopreserved cells.
Purpose of the Study:
- To investigate CD62L and CD45RA expression on fresh T-cells (CD4+ and CD8+) in NTZ-treated MS patients.
- To correlate T-cell subset expression with estimated risk of developing PML.
Main Methods:
- Prospective enrollment of 74 MS patients, with 62 receiving NTZ.
- Stratification of patients into low, intermediate, and high PML risk groups.
- Flow cytometry analysis of circulating naive and memory T-cell subsets in fresh blood.
Main Results:
- No correlation was found between CD62L+ CD4+ T-cell percentage and PML risk.
- A significant increase in CD8+ CD62L- CD45RA- effector memory T-cells (TEM) percentage and count was observed in the high-risk PML group.
- One high-risk patient with increased CD8+ TEM and CD62L+ CD4+ T-cells developed PML six months post-sampling.
Conclusions:
- CD8+ TEM cells show potential as a surrogate marker for PML risk in NTZ-treated MS patients.
- Further investigation in larger studies is warranted to validate CD8+ TEM cells as a predictive biomarker.
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