Dynamics of T cell repertoire renewal following autologous hematopoietic stem cell transplantation in multiple sclerosis
| Autor: | Josefine Ruder, María José Docampo, Jordan Rex, Simon Obahor, Reza Naghavian, Antonia M.S. Müller, Urs Schanz, Ilijas Jelcic, Roland Martin |
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| Přispěvatelé: | University of Zurich, Martin, Roland |
| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Science Translational Medicine. 14 |
| ISSN: | 1946-6242 1946-6234 |
| Popis: | Autologous hematopoietic stem cell transplantation (aHSCT) is a highly effective treatment of multiple sclerosis (MS). It depletes autoreactive cells and subsequently renews adaptive immune cells. The possible proinflammatory potential of surviving T cells early after aHSCT has not been studied. Here, we 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. Early after aHSCT, naïve T cells are barely detectable, whereas effector memory (EM) T cells quickly reconstitute to pre-aHSCT values. 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. We find a median TCR repertoire overlap of 26% between the early post-aHSCT EM CD4+T cells and pre-aHSCT, indicating persistence of EM CD4+T cells early after transplantation. The EM CD4+TCR repertoire overlap declines to 15% at 12 months after aHSCT, whereas the naïve TCR repertoire entirely renews. HLA-DR–associated EM CD4+T cell reactivity toward MS-related antigens decreased after aHSCT, whereas reactivity toward EBV increased. 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. |
| Databáze: | OpenAIRE |
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