Detailed below is a third achievement the Immune Tolerance Network (ITN) recently presented at the Member Society Symposium at the Federation of Clinical Immunology Societies (FOCiS) meeting, and how this work fits in with the broader pursuit of tolerance in transplantation.
TCR Repertoire Studies in ITN Trial of Autologous Hematopoietic Transplantation in MS
Autologous hematopoietic stem cell transplantation (HSCT), traditionally used to treat blood cancers, has recently been used as a method in autoimmune patients to “reset” the immune system in a non-autoreactive manner. This was the goal of the ITN’s HALT-MS study: to suppress inflammation in severe multiple sclerosis patients through immune regeneration via HSCT. The ITN employed a series of assays to phenotype the T cell repertoire post treatment. Paolo Muraro, MD, PhD (Imperial College London) presented data indicating that T cell receptor (TCR) diversity on CD4 and CD8 cells is lower at two months post-transplant in patients who failed treatment, raising the question as to whether TCR diversity may be an indication of future success or failure. Although it is too early to determine correlation with treatment effect, these analyses showed remarkable patient variation in persistence and frequency of the dominant baseline clones in both the CD4 and CD8 compartments. Future in-depth comparisons of the TCR repertoire in the treatment failures vs. full responders will help reveal mechanisms and markers of tolerance.