Autologous stem cell transplantation aids autoimmune patients by functional renewal and TCR diversification of regulatory T cells

Abstract

Key Points Autologous HSCT induces functional renewal of regulatory T cells as well as a strong Treg TCR diversification in autoimmune patients. Adding regulatory T cells to the graft does not lead to additional clinical improvement but results in delayed donor T-cell reconstitution.

Immune rebound associates with a favorable clinical response to autologous HSCT in systemic sclerosis patients

“…62,63 Expansion of the Treg compartment following transplantation starts with lymphopenia-induced proliferation, followed by thymic generation of natural Tregs. 64 This mechanism appears to be nondisease-specific and has been reported in other autoimmune diseases. 14,30,31,[36][37][38][65][66][67] Indeed, as already shown in multiple sclerosis, 37 our group of responder SSc patients experienced significantly increased expression of regulatory molecules after AHSCT, when compared with nonresponders.…”

Haematopoietic stem cell transplantation in autoimmune diseases: From basic science to clinical practice

“…Alongside this, in MS and some CTDs there is evidence of thymic processing leading to restoration a naïve immune system, T cell receptor diversity and loss of putative disease specific dominant clones, particularly in the T-regulatory compartment [115,118]. Beyond the fundamental changes, autologous HSCT has been shown to influence downstream changes, such as reversal of fibrosis and vasculature in SSc [122]. Such data support the hypothesis that in some diseases autologous HSCT results in a 'resetting' or 're-booting' of the immune system, resulting in a reduction or cessation in autoinflammation, and, in some patients allowing repair of endorgan damage [118,123,124].…”

Evolution, trends, outcomes, and economics of hematopoietic stem cell transplantation in severe autoimmune diseases

“…6,[44][45][46] In conjunction with both prospective and registry studies, mechanistic studies have been progressively produced. [47][48][49][50] The recent publication of guidelines for studies of immune reconstitution studies and biobanking provides the necessary framework for further development of mechanistic studies. 51 More standardized approaches to immune monitoring should facilitate correlative studies with outcomes of HSCT and potentially enable biomarkers to be developed to assist with patient selection and treatments.…”