Relapsing-remitting central nervous system autoimmunity mediated by GFAP-specific CD8 T cells

Area of Science:

• Neuroimmunology
• Autoimmune Diseases

Background:

• Multiple sclerosis (MS) is traditionally viewed as a CD4 T cell-mediated autoimmune disease affecting CNS white matter.
• Recent findings highlight CD8 T cell involvement and gray matter lesions in MS, suggesting broader autoimmune targets beyond myelin proteins.

Purpose of the Study:

• To investigate the role of CD8 T cells reactive to glial fibrillary acidic protein (GFAP) in central nervous system (CNS) autoimmunity.
• To determine how different T cell-triggering events influence the presentation and pathology of CNS autoimmune diseases.

Main Methods:

• Utilized GFAP-specific CD8 TCR-transgenic (BG1) mice to model CNS autoimmunity.
• Investigated spontaneous and virally triggered autoimmune responses mediated by GFAP-specific CD8 T cells.
• Assessed the influence of B cells on disease progression and pathology.

Main Results:

• Spontaneous infiltration of CNS gray and white matter by GFAP-specific CD8 T cells led to relapsing-remitting autoimmunity in BG1 mice.
• The presence of polyclonal B cells modulated the frequency, severity, and remissions of the spontaneous disease.
• A viral trigger caused GFAP-specific CD8 T cells to target meninges and perivascular spaces, resulting in acute CNS disease.

Conclusions:

• CD8 T cells reactive to CNS antigens like GFAP can drive distinct forms of autoimmune pathology.
• The nature of the initial T cell-triggering event is a critical determinant of CNS autoimmune disease presentation and severity.