Introduction: Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS), where the immune system plays a crucial role. Autologous haematopoietic stem cell therapy (AHSCT) induces a long-lasting remission of disease activity in patients with relapsingremitting (RR)-MS. Objectives/Aims: Our study aims at identifying the mechanisms underlying the suppression of MS inflammation after AHSCT. Methods: Ten patients with active RR-MS who had failed disease-modifying treatments received AHSCT with a BEAM (carmustine, etoposide, cytarabine and melphalan) and rabbit anti-thymocyte globulin (ATG) as conditioning. B and T lymphocyte reconstitution was studied in PBMCs by multiparametric flow cytometry before and at months 6 and 12 after AHSCT. Results: In the CD4 subset, naïve CD4 T cells decreased at 6 months and returned to baseline at 12 months post-AHSCT, while IFNg-producing effector memory (EM) and terminally differentiated effector memory (TEMRA) increased at 6 months and reached the baseline at 12 months post-AHSCT. In the CD8 subset, naïve CD8 T cells and MAIT were lower than the baseline during follow-up while T memory stem cells (TSCM) decreased only at 12 months post-AHSCT. Granzyme b and interferon g-producing EM increased at 6 and 12 months, and granzyme b-producing EMRA and central memory (CM) increased at 12 months post-AHSCT. In the B cell compartment, transitional and naive B cells increased at 6 and 12 months while switched memory B cells decreased at 6 months post-HSCT Conclusion: The T cell compartment after AHSCT shows the expansion of EM and CM and TEMRA supporting a potentially antigen-driven differentiation and maturation. The B cell compartment shows an expansion of regulatory and immature B cells. The observed changes suggest that T cell regeneration postAHSCT occurs under increased regulatory B cell control promoting immune tolerance.
immune reconstitution following autologous haematopoietic stem cell therapy in patients with active relapsing-remitting multiple sclerosis
Cencioni, MTConceptualization
;
2023-01-01
Abstract
Introduction: Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS), where the immune system plays a crucial role. Autologous haematopoietic stem cell therapy (AHSCT) induces a long-lasting remission of disease activity in patients with relapsingremitting (RR)-MS. Objectives/Aims: Our study aims at identifying the mechanisms underlying the suppression of MS inflammation after AHSCT. Methods: Ten patients with active RR-MS who had failed disease-modifying treatments received AHSCT with a BEAM (carmustine, etoposide, cytarabine and melphalan) and rabbit anti-thymocyte globulin (ATG) as conditioning. B and T lymphocyte reconstitution was studied in PBMCs by multiparametric flow cytometry before and at months 6 and 12 after AHSCT. Results: In the CD4 subset, naïve CD4 T cells decreased at 6 months and returned to baseline at 12 months post-AHSCT, while IFNg-producing effector memory (EM) and terminally differentiated effector memory (TEMRA) increased at 6 months and reached the baseline at 12 months post-AHSCT. In the CD8 subset, naïve CD8 T cells and MAIT were lower than the baseline during follow-up while T memory stem cells (TSCM) decreased only at 12 months post-AHSCT. Granzyme b and interferon g-producing EM increased at 6 and 12 months, and granzyme b-producing EMRA and central memory (CM) increased at 12 months post-AHSCT. In the B cell compartment, transitional and naive B cells increased at 6 and 12 months while switched memory B cells decreased at 6 months post-HSCT Conclusion: The T cell compartment after AHSCT shows the expansion of EM and CM and TEMRA supporting a potentially antigen-driven differentiation and maturation. The B cell compartment shows an expansion of regulatory and immature B cells. The observed changes suggest that T cell regeneration postAHSCT occurs under increased regulatory B cell control promoting immune tolerance.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
