T cells have the ability to identify an enormous range of self and foreign epitopes. The activation of APCs in recipient tissues is one of the important factors responsible for GvHD. This delays thymic recovery influences the dynamics of immune reconstitution and thus the time-dependent recovery of the TCR repertoire. Conditioning regiment involving chemotherapy and radiotherapy leads to the damage of the thymus. GvHD prophylaxis requires immunosupressive therapies that influence the TCR repertoire, by depleting T cells. Infections post transplant influence the TCR diversity due to an increase in antigen-specific TCRs. They all influence the diversity of the recipient TCR repertoire. Other factors are the history of infections of the donor as well as the post-transplant infections of the recipient and the age of both, donor and recipient. Donor–recipient factors include transplant regimen, source of graft and HLA matching status between donor and recipient. The factors altering TCR dynamics post allo-SCT can be divided into donor-recipient factors, the GvHD prophylaxis post-transplant and the conditioning regimen prior to transplant. Here, we review the AIRR sequencing studies on T cells in GvHD post HSCT. The TCR repertoire is likely a footprint of the complex pathophysiology of GvHD, which is shaped by different factors affecting the type of the alloantigen like graft source, HLA matching status, infections, GvHD prophylaxis etc. In this review, we focus on T cell receptor (TCR) sequencing studies. Application of NGS to profile dynamics in adaptive immunity includes the adaptive immune receptor repertoire (AIRR) sequencing studies of both, B and T cell receptors. Technologies such as next-generation sequencing (NGS) are promising tools to obtain genetic information and further insights into the T cell pathophysiology of GvHD. There is a need to better understand the targets and cellular basis of T cell alloreactivity and its role in the clinical outcome following allo-HSCT. The activation of donor alloreactive T cells leads to a clonal expansion of selected T cells and to the attraction of other proinflammatory effector cells. The general concept is that GvHD is initiated by the activation of donor alloreactive T cells, which recognise host-specific histocompatibility antigens presented on host antigen-presenting cells. The extent of GvHD can vary from mild signs of inflammation to severe and life-threatening forms in advanced GvHD. Both types of GvHD may overlap clinically, leading to relevant mortality, and cGvHD can greatly affect the quality of life of long-term survivors after transplantation. Chronic GvHD (cGvHD) has different clinical features and may occur de novo after days 80–100 or develop as secondary disease in patients with acute GvHD. Per definition, acute GvHD (aGvHD) usually occurs within the first months following transplantation. However, a major complication following allo-HSCT is graft-versus-host disease (GvHD). This desired immune reaction is the graft-versus-leukaemia effect. Donor HSC engraftment and the transferred donor immune system contribute to the eradication of remaining malignant cells. Allo-HSCT involves the transfer of haematopoietic stem cells (HSCs) obtained from related or unrelated donors to patients. Similar content being viewed by othersĪllogeneic haematopoietic stem cell transplantation (allo-HSCT) is a well-established treatment procedure for haematologic diseases such as high-risk acute leukaemia. This review provides insights into current studies of the TCR repertoire in GvHD and potential future clinical implications of TCR sequencing. Monitoring the frequency and specificities of specific TCR clonotypes longitudinally in different conditions and specimens (peripheral blood, GvHD-affected tissue samples) can provide insights into factors modulating immune reactions following allogeneic transplantation and will help to understand the underlying mechanisms mediating GvHD. Monitoring the changes in the TCR repertoire using TCR sequencing can provide an indication of the dynamics of a T cell population. The composition of TCRs within a T cell population defines the TCR repertoire of an individual, and this repertoire represents exposure to self and non-self proteins. T cells identify a broad range of antigens and mediate the immune response through receptors on their surfaces (T cell receptors, TCRs). T cells are implicated in initiating GvHD. GvHD can occur in almost every tissue, with the skin, liver, and intestines being the mainly affected organs. Graft-versus-host disease (GvHD) remains one of the major complications following allogeneic haematopoietic stem cell transplantation (allo-HSCT).
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