It is well documented that multiple sclerosis patients often struggle with finding drugs that effectively treat and manage the progression of the disease. While there is a wide range of different disease altering and interferon-based drugs for the treatment of multiple sclerosis’ various disease types, many patients find that standard treatments — particularly in the secondary progressive MS phase of the disease — are not effective. However, a new study led by the Immune Tolerance Network (ITN) has revealed how T cells behave and expand their diversity following an autologous stem cell transplant, which is a treatment for MS, and an alternative to standard drug therapy.
MS is a chronic disease wherein patients’ immune systems attack their own central nervous system, including the brain, spinal cord and optic nerves, causing paralysis, blindness, and numbness in the limbs. To prevent the immune system from attacking the central nervous system, patients potentially can reprogram their own immune system to function normally by transplanting their own stem cells.
ITN investigators analyzed the diversity of T cell receptors (TCR) in CD4+ and CD8+ T cells at the point of pre-transplant, 2 months post-transplant, and 12 months post-transplant, with a high-throughput, deep-sequencing technology (Adaptive Biotechnologies, ImmunoSEQTM Platform) and conventional flow cytometry.
Results showed that CD8+ T cell sequences at pre-transplant were not effectively eradicated after the transplant. In contrast, CD4+ T cell clones were undetectable at 12 months post-transplant and predominantly replaced with new clones.
These results suggest the possibility that the diversity of T cells in the early reconstitution of post-transplant conditions could be important for establishing immune tolerance, and it could be associated with clinical outcomes from ITN’s HALT-MS study. In 24 patients with relapsing-remitting MS who received an autologous stem cell transplant, 19 patients showed positive responses for the treatment, and 4 patients did not. The 19 patients were found to have more diversity of T cells at 2 months post-transplant, compared to non-responders.
The study was published in the Journal of Clinical Investigation, and the results could give us deeper insights into understanding immune tolerance development.