Search results for "host disease"
showing 10 items of 126 documents
Donor and host B cell-derived IL-10 contributes to suppression of graft-versus-host disease
2014
Graft-versus-host disease (GvHD) is a frequent life-threatening complication following allogeneic HSC transplantation (HSCT). IL-10 is a regulatory cytokine with important roles during GvHD, yet its relevant sources, and mode of action, remain incompletely defined in this disease. Using IL-10-deficient donor or host mice (BALB/c or C57BL/6, respectively) in a MHC-mismatched model for acute GvHD, we found a strongly aggravated course of the disease with increased mortality when either donor or host cells could not produce this cytokine. A lack of IL-10 resulted in increased allogeneic T-cell responses and enhanced activation of host DCs in spleen and MLNs. Remarkably, IL-10 was prominently p…
Preemptive Transfer of GMP-Grade CD8-Depleted Donor Lymphocytes after T-Cell Depleted Reduced-Intensity Transplantation.
2005
Abstract The combination of fludarabin (150mg/m2) / melphalan (140mg/m2) based reduced-intensity allo-transplantation (RIT) with in vivo T-cell depletion (TCD) by the anti-CD52 antibody alemtuzumab (100mg) has demonstrated efficient engraftment and reduced graft-versus-host disease (GVHD) (Kottaridis et al., Blood 2000). However, the slow lymphocyte recovery following this protocol is associated with reduced anti-infectious and antitumor immunity. In an attempt to improve immune-reconstitution after TCD / RIT, we investigated the early preemptive use of CD8-depleted donor lymphocyte infusions (DLIs). For CD8 depletion of donor leukaphereses, a new depletion protocol using clinical grade CD8…
Graft-Versus-Host Disease or Infection: Rapid Detection of HLA Mismatch-Reactive T Cells Ex Vivo Can Facilitate Diagnosis and Guide Therapy after All…
2007
Abstract Diagnosis of graft-versus-host disease (GVHD) is mainly based on clinical features and on tissue biopsies. However, clinicians and pathologists are well aware of cases, in which GVHD cannot be distinguished from infections arising from severe immunodeficiency after allogeneic stem-cell transplantation (SCT). This may pose a deep therapeutic dilemma of whether to modify immunosuppressive treatment or to use donor lymphocyte infusion (DLI) for promoting anti-microbial immunity. We observed a 68-year-old patient with myelodysplastic syndrome who developed acute GVHD grade II of skin and gut at d+16 after T-cell depleted reduced-intensity SCT (Fig. 1). GVHD was confirmed by histology a…
Impact of DLI after In Vivo T-Cell-Depletion: Prophylactic CD8 Depleted or Preemptive CD3pos DLI?
2016
Abstract Introduction: The combination of reduced-intensity conditioning (RIC) with in vivo T-cell depletion by alemtuzumab prior to hematopoietic stem cell transplantation (HSCT) has demonstrated efficient engraftment and reduced graft-versus-host disease (GVHD). However, this regimen is associated with slow lymphocyte recovery leading to a delayed anti-infectious and anti-malignant immunity. DLI can be used to improve immune reconstitution. Here we investigate on the impact of different DLI: prophylactic CD8-depleted DLI vs preemptive non-depleted DLI. Methods: 256 patients with different hematologic malignancies were planned for treatment with DLI after allogeneic HSCT following reduced …
Leishmaniasis, contact hypersensitivity and graft-versus-host disease: understanding the role of dendritic cell subsets in balancing skin immunity an…
2010
Dendritic cells (DC) are key elements of the immune system. In peripheral tissues, they function as sentinels taking up and processing antigens. After migration to the draining lymph nodes, the DC either present antigenic peptides by themselves or transfer them to lymph node-resident DC. The skin is the primary interface between the body and the environment and host's various DC subsets, including dermal DC (dDC) and Langerhans cells (LC). Because of their anatomical position in the epidermis, LC are believed to be responsible for induction of adaptive cutaneous immune responses. The functions of LC and dDC in the skin immune system in vivo are manifold, and it is still discussed controvers…
Protection of Mice from Acute Graft-versus-Host Disease Requires CD28 Co-stimulation on Donor CD4+ Foxp3+ Regulatory T Cells
2017
Acute graft-versus-host disease (aGvHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell plus T cell transplantation (allo-HSCT). In this study, we investigated the requirement for CD28 co-stimulation of donor CD4\(^{+}\) conventional (CD4\(^{+}\)CD25\(^{-}\)Foxp3\(^{-}\), Tconv) and regulatory (CD4\(^{+}\)CD25\(^{+}\)Foxp3\(^{+}\), Treg) T cells in aGvHD using tamoxifen-inducible CD28 knockout (iCD28KO) or wild-type (wt) littermates as donors of CD4\(^{+}\) Tconv and Treg. In the highly inflammatory C57BL/6 into BALB/c allo-HSCT transplantation model, CD28 depletion on donor CD4\(^{+}\) Tconv reduced clinical signs of aGvHD, but did not significantly pro…
Impact of Prophylactic CD8-Depleted Donor-Lymphocyte Infusions After Allogeneic Hematopoietic Stem Cell Transplantation and Alemtuzumab Mediated T-Ce…
2011
Abstract Abstract 4109 We have previously demonstrated that the application of CD8-depleted donor-lymphocyte infusions (DLI) is feasible after reduced-intensity conditioning and in vivo T-cell depletion by alemtuzumab. DLI overcome slow lymphocyte recovery associated with alemtuzumab-administration and improve anti-infectious immunity and reliably convert a decreasing T-cell chimerism (Meyer et al. Blood 2007 & BMT 2010). Here we provide clinical follow up data of 117 patients with different hematological diseases and a median observation time of 1 year (range, 1–86 months) post hematopoietic stem cell transplantation (HSCT). The majority of patients either suffered from an acute leukem…
Management of oral Graft versus Host Disease with topical agents: a systematic review
2015
Background: Oral Graft-versus-Host Disease (oGvHD) is a common complication of haematopoietic stem cell transplantation. Choosing the right topical application to be used intra orally can be a challenge. Consequently, the aim of this work is to review the effectiveness and safety of topical agents currently used in the management of the inflammatory mucosal lesions encountered in oGVHD. Material and Methods: We carried out electronic searches of publications up to May 2015 of the databases Pubmed, National Library of Medicine’s Medline, Embase and the Cochrane Central Register of Controlled Clinical trials to identify potentially relevant studies (keywords: “oral”, “graft”, “versus”, “host”…
Control Of Organ Transplant-Associated Graft-versus-Host Disease By Activated Host Lymphocyte Infusions
2004
Background Prolonged persistence of donor-derived T cells after organ transplantation has been proposed to improve long-term allograft survival. However, surviving transplant-derived T cells are also able to mediate devastating graft-versus-host disease (GvHD). Currently, GvHD after organ transplantation is usually refractory to conventional therapy and the disease outcome fatal. Methods Graft-reactive host T cells were generated ex vivo from a patient suffering from a severe and refractory liver-transplant-associated GvHD. To control GvHD, activated alloreactive host T cells were repetitively retransferred into the patient (activated host lymphocyte infusion [aHLI]). Results Adoptive trans…
Characteristics of patients with mucopolysaccharidosis type II who have received a bone marrow transplant: Data from the Hunter Outcome Survey
2019
Mucopolysaccharidosis type II (MPS II Hunter syndrome) is a rare, life-limiting, X-linked lysosomal storage disease. The Hunter Outcome Survey (HOS) is a Shire-sponsored, global, observational registry initiated in 2005 that collects real-world data on the natural history of MPS II and long-term treatment with enzyme replacement therapy (ERT) with idursulfase. Patients receiving other forms of pharmacological ERT are excluded from HOS but individuals who have received a bone marrow transplant (BMT) may be enrolled. This analysis examined the characteristics of 36 male patients in HOS from Europe and North America who had received a BMT (March 2018 data). In total, 22 patients (61.1%) were E…