HLA-B7-restricted EBV-specific CD8+ T cells are dysregulated in multiple sclerosis

Area of Science:

• Immunology
• Virology
• Neuroscience

Background:

• Epstein-Barr virus (EBV) is a suspected factor in multiple sclerosis (MS) pathogenesis.
• CD8(+) T cell responses are crucial for viral control.
• Dysregulation of EBV-specific CD8(+) T cells may impair viral control in MS patients.

Purpose of the Study:

• To investigate the hypothesis that EBV-specific CD8(+) T cell responses are dysregulated in MS patients.
• To analyze HLA class I-restricted EBV- and CMV-specific CD8(+) T cell responses in MS patients and controls.
• To assess the functional capacity of these T cells.

Main Methods:

• Analysis of HLA-A2-, HLA-B7-, and HLA-B8-restricted EBV- and CMV-specific CD8(+) T cell responses using tetramer technology.
• Assessment of cytolytic granule content and cytotoxic activity.
• Comparison of T cell responses between a large cohort of MS patients and control subjects.

Main Results:

• MS patients exhibited altered prevalence of HLA-A2 and HLA-B7 alleles.
• A higher prevalence of HLA-B*0702/EBV(RPP)-specific CD8(+) T cells was observed in HLA-B7(+) MS patients.
• The magnitude of HLA-B*0702-restricted EBV- and CMV-specific CD8(+) T cell responses was reduced in MS patients.
• Impaired IL-2 production, perforin and granzyme B expression, and cytotoxicity were noted in EBV-specific CD8(+) T cells after peptide stimulation.

Conclusions:

• The HLA-B*0702-restricted viral-specific CD8(+) T cell response, particularly to EBV, is dysregulated in MS patients.
• The increased frequency of the HLA-B7 allele in MS patients, coupled with impaired EBV-specific T cell function, warrants further investigation.
• These findings suggest a potential mechanism linking EBV infection, HLA-B7, and MS pathogenesis.