Ocrelizumab Alters Cytotoxic Lymphocyte Function While Reducing EBV-Specific CD8⁺ T-Cell Proliferation in Patients...

Area of Science:

• Immunology
• Neuroimmunology
• Cellular Biology

Background:

• B cells play a recently elucidated role in the pathogenesis of relapsing multiple sclerosis (R-MS).
• Anti-CD20 monoclonal antibodies, like ocrelizumab, are effective therapies for R-MS.
• The impact of anti-CD20 therapy on other immune cells, beyond B cells, is not fully understood.

Purpose of the Study:

• To investigate the effects of ocrelizumab on cytotoxic lymphocytes (CD8+ T and NK cells) in R-MS patients.
• To assess the impact of ocrelizumab on Epstein-Barr virus (EBV)-specific immune responses.
• To explore potential indirect mechanisms of ocrelizumab's therapeutic efficacy.

Main Methods:

• Prospective study of 41 R-MS patients initiating ocrelizumab.
• Blood samples collected pre-treatment and at 6 and 12 months post-treatment.
• Analysis of immune cell phenotype, cytotoxic functions, and EBV-specific T-cell and NK cell proliferation.

Main Results:

• Ocrelizumab depleted circulating B cells.
• Reduced expression of activation/migratory markers on CD8+ T and NK cells.
• Decreased in vitro cytotoxic activity of CD8+ T and NK cells.
• Selective reduction in CD8+ T-cell proliferation against EBV peptides.

Conclusions:

• Ocrelizumab affects the cytotoxic functions of CD8+ T and NK cells, not just B cells.
• This modulation of cytotoxic cells may contribute to ocrelizumab's therapeutic efficacy in MS.
• Reduced cross-reactivity of these cells against myelin antigens is a potential mechanism.