Interplay between T-cells and Neurons: The T-cells are the winner

Extensive white matter lesions are seen in a patient with Multiple Sclerosis that are present in the periventricular region of the brain where neural stem cells usually present suggesting the possibility that these lesions may affect neurogenesis.

Focal infiltrates of T cells are commonly found in brain of patients with Multiple Sclerosis and are an important factor in triggering a relapse in these patients. These focal areas of pathology are called lesions where there maybe loss of brain tissue from myelin and neuronal/axonal injury. This loss of neurons or axon may result in black holes seen on MRI scans. Additionally there is a generalized progressive atrophy of the brain in patients with Multiple Sclerosis that starts early in the disease.

For these reasons, we have developed a research project to determine if activated T cells can cause neuronal injury and if these cells can release neurotoxic substances.

We have found that activated T cells release several neurotoxic substances, one of which is called granzyme B. We are now investigating the cell surface receptors on neurons that granzyme B interacts with, the secondary signaling pathways triggered by granzyme B and developing pharmacological means of blocking the effects of granzyme B.