Distinct Effects of Autologous Hematopoietic Stem Cell Transplantation on T Cell Composition and Profile in Refractory Crohn's Disease

Abstract

BACKGROUND: Autologous hematopoietic stem cell transplantation (aHSCT) holds promise as a therapeutic strategy in patients with severe chronic inflammatory conditions that are refractory to conventional treatment, including Crohn's disease. The success of aHSCT is thought to be grounded in resetting the break in immunological tolerance, but the exact mechanisms underlying its effects remain incompletely understood. METHODS: We followed the immune reconstitution of nine patients with severe refractory Crohn's disease before and after aHSCT, ranging from 1 month until 2 + years follow-up. We used flow cytometry on peripheral blood mononuclear cells and intestinal biopsy samples, as well as Olink on plasma samples. RESULTS: In line with previous research, we observed a strong change in the peripheral T cell subset composition from 1 month after transplantation, with a reversal of the CD4+/CD8+ ratio and a reduction of naïve over effector memory T cells (T-EM). Non-responders appeared distinct by retaining a higher CD4+/CD8+ ratio and higher naïve over T-EM frequencies. These differences could already be discerned at baseline, before transplantation. Functionally, we observed only minimal changes in the peripheral T cell profile related to inflammation and homing, but a small increase in regulatory markers. Remarkably, the local intestinal T cell composition did not mirror changes in the periphery, with an increased CD4+/CD8+ ratio in intestinal biopsies post-aHSCT. CONCLUSIONS: Autologous hematopoietic stem cell transplantation had pronounced effects on the peripheral T cell composition, especially in responders. Changes in T cell subset composition were more pronounced than changes in the functional T cell profile.