Abstract
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, in which autoreactive T and B cells play important roles. Other lymphocytes such as NK cells and innate-like T cells appear to be involved as well. To name a few examples, CD56bright NK cells were described as an immunoregulatory NK cell subset in MS while innate-like T cells in MS were described in brain lesions and with proinflammatory signatures. Autologous hematopoietic stem cell transplantation (aHSCT) is a procedure used to treat MS. This procedure includes hematopoietic stem/progenitor cell (HSPC) mobilization, then high-dose chemotherapy combined with anti-thymocyte globulin (ATG) and subsequent infusion of the patients own HSPCs to reconstitute a functional immune system. aHSCT inhibits MS disease activity very effectively and for long time, presumably due to elimination of autoreactive T cells. Here, we performed multidimensional flow cytometry experiments in peripheral blood lymphocytes of 27 MS patients before and after aHSCT to address its potential influence on NK and innate-like T cells. After aHSCT, the relative frequency and absolute numbers of CD56bright NK cells rise above pre-aHSCT levels while all studied innate-like T cell populations decrease. Hence, our data support an enhanced immune regulation by CD56bright NK cells and the efficient reduction of proinflammatory innate-like T cells by aHSCT in MS. These observations contribute to our current understanding of the immunological effects of aHSCT in MS.
Highlights
Over 2.5 million people worldwide are affected with multiple sclerosis (MS), a chronic, demyelinating disease of the central nervous system (CNS), which is usually diagnosed at the young age of 20-40 years
With a panel that allowed us to differentiate innate-like T cells like mucosa-associated invariant T (MAIT) cells, NKT(-like) cells and gd T cells from the innate natural killer (NK) cell subpopulations, we studied their immune reconstitution in MS patients post-Autologous hematopoietic stem cell transplantation (aHSCT) in seven individuals of our cohort
In this study we describe the immune reconstitution dynamics of NK and innate-like T cells after aHSCT in MS patients
Summary
Over 2.5 million people worldwide are affected with multiple sclerosis (MS), a chronic, demyelinating disease of the central nervous system (CNS), which is usually diagnosed at the young age of 20-40 years. A large body of evidence supports the NK and Innate-Like T Cells in aHSCT in MS importance of T cells in the pathogenesis of MS, especially of CD4+ T cells [1]. Available data indicate that innate immune cells including innate lymphoid cells (ILCs) and innate-like T and B lymphocytes are involved in MS pathogenesis [5]. NK cell activation and killing is controlled by multiple NK receptors with a balance between activating receptors e.g. for Fc region of IgG leading to ADCC, and inhibitory receptors recognizing e.g. MHC, resulting in the attack of cells with low or absent MHC expression [6]. Certain populations might enhance disease progression by harming the myelin sheath via ADCC, while others can have immunoregulatory effects like killing activated T cells [9]
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