Engineered T cell therapy for central nervous system injury.

Area of Science:

• Neuroscience
• Immunology
• Cell Biology

Background:

• Central nervous system (CNS) injuries affect millions globally, with limited effective treatments.
• Peripheral immune cells, including T cells, infiltrate injury sites, but their specific roles and antigen recognition remain unclear.
• This knowledge gap hinders the development of immune-based cellular therapies for CNS injuries.

Purpose of the Study:

• To investigate the clonal expansion and antigen specificity of T cells at CNS injury sites.
• To develop and evaluate engineered T cells for potential neuroprotective therapies.

Main Methods:

• Single-cell RNA sequencing to analyze T cell populations in mouse and human spinal cord injury models.
• T cell receptor (TCR) reconstitution using mRNA technology to engineer transiently autoimmune T cells.
• Assessment of neuroprotective efficacy in CNS injury models.

Main Results:

• Demonstrated clonal expansion of T cells associated with spinal cord injuries in both mice and humans.
• Identified CD4+ T cell clones in mice recognizing self-peptides from myelin and neuronal proteins.
• Engineered T cells exhibited significant neuroprotective effects, partly through myeloid cell modulation via Interferon-gamma (IFNγ).

Conclusions:

• Elucidated the mechanistic basis of neuroprotective functions of injury-responsive T cells.
• Established the antigen specificity of T cells in CNS injury environments.
• Paved the way for developing novel T cell-based therapies for CNS injuries.