Intrathecal CD8⁺CD20⁺ T Cells in Primary Progressive Multiple Sclerosis

Area of Science:

• Neuroimmunology
• Multiple Sclerosis Pathogenesis
• T cell Biology

Background:

• Intrathecal inflammation is evident in primary progressive multiple sclerosis (PPMS).
• Current immunomodulatory treatments show limited success in PPMS.
• The role of CD20+ T cells in PPMS remains to be fully elucidated.

Purpose of the Study:

• To investigate the involvement of CD20+ T cells in PPMS.
• To assess the effect of dimethyl fumarate on CD20+ T cells in the cerebrospinal fluid (CSF) of PPMS patients.

Main Methods:

• Observational, case-control study design.
• Flow cytometry analysis of blood and CSF CD20+ T cells.
• ELISA for myelin basic protein and neurofilament light chain.
• MRI assessment of brain lesions and volumes.
• Treatment with dimethyl fumarate or placebo for 48 weeks.

Main Results:

• Increased percentage of CD20+ T cells in the blood and CSF of untreated PPMS patients.
• Higher frequency of CD8+CD20+ T cells in CSF correlated with markers of disease activity and brain atrophy.
• CD8+CD20+ T cells were associated with new T2 lesion development.
• Dimethyl fumarate treatment reduced total T cells in CSF but did not affect CD20+ T cells.

Conclusions:

• Intrathecal CD8+CD20+ T cells are associated with white matter injury and thalamic atrophy in PPMS.
• CD8+CD20+ T cells likely play a role in PPMS immunopathogenesis.
• The limited efficacy of dimethyl fumarate in PPMS may stem from its inability to suppress CSF CD8+CD20+ T cells.