Study Examines Immune System of MS Patients Who Undergo Stem Cell Transplant

Stem cell therapy is known to help improve an MS patient’s symptoms and slow down the progression of the disease. In fact, stem cell transplants have shown higher remission rates compared to the available medications and those with MS who get stem cell transplants might get “potent disease control benefits” that last up to 10 years with no need for additional medication.

However, there has been little research in what happens to the immune system of someone with MS who undergoes such a stem cell transplant

That led researchers in Zurich, Switzerland, to look at how the immune system of a person with MS undergoing a stem cell transplant is affected, conducting a new study on T-cells1.

Roland Martin, M.D., and his colleagues profiled the T cells of 27 patients who had received autologous hematopoietic stem cell transplantation.

“Adults have very little functioning tissue left in the thymus, but after a transplant, the organ appears to resume its function and ensures the creation of a completely new repertoire of T-cells, which evidently do not trigger MS or cause it to return,” said study co-author Roland Martin, M.D., professor for neurology and neuroimmunology at the University of Zürich.

He explained how previous studies have showed a slow return of naïve T cells after an autologous hematopoietic stem cell transplantation (aHSCT), but the dynamics of new and surviving T cells after aHSCT remain to be elucidated.

In the study, which was published in Science Translational Medicine, the research team analyzed samples from patients with MS after aHSCT and revealed that whereas effector memory T cells quickly reconstitute, naïve T cells displayed a slower complete renewal.

Martin and his colleagues also performed a complete characterization of the renewed T cell population.

Overall, the team examined the dynamics of new and surviving T cells in 27 patients after aHSCT by multidimensional flow cytometry, T cell receptor (TCR) sequencing, specificity testing, telomere length profiling and HLA genotyping. The analysis was done before, during and up to two years after treatment. This allowed the researchers to track how quickly the different types of immune cells regenerated.

“Early after aHSCT, naïve T cells are barely detectable, whereas effector memory (EM) T cells quickly reconstitute to pre-aHSCT values,” the study authors wrote. “EM CD4+ T cells early after aHSCT have shorter telomeres, have higher expression of senescence and exhaustion markers, and proliferate less than those before aHSCT.”

Therefore, Martin and his team concluded that a median TCR repertoire overlap of 26% between the early post-aHSCT EM CD4+ T cells and pre-aHSCT, indicates persistence of EM CD4+ T cells early after transplantation.

Furthermore, the EM CD4+ TCR repertoire overlap decreased to 15% at 12 months after aHSCT, while the naïve TCR repertoire renews entirely.

“HLA-DR–associated EM CD4+ T cell reactivity toward MS-related antigens decreased after aHSCT, whereas reactivity toward EBV increased,” he explained. “Our data show substantial survival of pre-aHSCT EM CD4+ T cells early after transplantation but complete renewal of the T cell repertoire by nascent T cells later.”

According to Martin, the results will provide a valuable resource for understanding the mechanisms mediating the efficacy of aHSCT in patients with MS.