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Low frequencies of central memory CD4 T cells in progressive multifocal leukoencephalopathy
Evelyn Dubois1, Christoph Ruschil1, Felix Bischof1
1Center of Neurology and Hertie Institute for Clinical Brain Research, University of Tübingen, Germany.
Objectives:
To assess alterations in the composition of peripheral immune cells in acute progressive multifocal leukoencephalopathy (PML).
Methods:
Fresh blood samples from 5 patients with acute PML and 10 healthy controls were analyzed by flow cytometry for naive, central memory and effector memory CD4 and CD8 T cells, B lymphocytes, plasma cells, memory B cells, plasma blasts, and natural killer (NK) cells. The frequency of central memory CD4 T cells was determined longitudinally during the course of PML in 2 patients.
Results:
The frequencies of naive, central memory and effector memory CD8 T cells, B cells, plasma cells, and NK cells were not altered in patients with PML. In contrast, the frequencies of naive CD4 T cells (p = 0.04) and central memory CD4 T cells (p < 0.00001) were reduced and the frequencies of effector memory CD4 T cells were increased (p = 0.01). Longitudinal analysis showed that this pattern was preserved in a patient with fatal PML outcome and restored in one patient who recovered from PML.
Conclusions:
These data indicate that PML is associated with reduced frequencies of peripheral central memory helper T cells but not with alterations in the frequencies of cytotoxic T cell populations, B lymphocytes, plasma cells, or NK cells.
Insights
Progressive multifocal leukoencephalopathy (PML) is linked to fewer helper T cells but normal cytotoxic T cells, B cells, and NK cells. Immune cell changes in PML patients may recover with treatment.
Area of Science:
- Neuroimmunology
- Immunology
- Virology
Background:
- Progressive multifocal leukoencephalopathy (PML) is a rare, severe demyelinating disease of the central nervous system.
- PML is caused by the JC virus (JCV) in immunocompromised individuals.
- Understanding immune cell alterations in PML is crucial for disease management.
Purpose of the Study:
- To investigate changes in peripheral immune cell composition in patients with acute PML.
- To compare immune cell profiles of PML patients with healthy controls.
Main Methods:
- Flow cytometry analysis of peripheral blood samples from 5 acute PML patients and 10 healthy controls.
- Quantification of various T cell subsets (naive, central memory, effector memory CD4 and CD8), B lymphocytes, plasma cells, memory B cells, plasma blasts, and NK cells.
- Longitudinal monitoring of central memory CD4 T cells in 2 PML patients.
Main Results:
- PML patients showed no significant alterations in CD8 T cells, B lymphocytes, plasma cells, or NK cells.
- A significant reduction in naive and central memory CD4 T cells was observed in PML patients (p = 0.04 and p < 0.00001, respectively).
- An increase in effector memory CD4 T cells was noted in PML patients (p = 0.01).
Conclusions:
- PML is associated with a specific depletion of peripheral central memory helper T cells.
- The observed immune cell alterations in PML do not involve cytotoxic T cells, B cells, plasma cells, or NK cells.
- Longitudinal data suggest immune cell patterns may be restored in recovering PML patients.
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