Host Dendritic Cells Alone Are Sufficient to Initiate Acute Graft-versus-Host Disease

Duffner, Ulrich; Maeda, Yoshinobu; Cooke, Kenneth R.; Reddy, Pavan; Ordemann, Rainer; Liu, Chen; Ferrara, James L.M.; Teshima, Takanori

doi:10.4049/jimmunol.172.12.7393

Cited by 220 publications

(176 citation statements)

References 34 publications

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“…Several mouse model experiments have revealed that transfer of IL-17-producing cells induced acute GVHD, [33][34][35] whereas in contrast there is a report 31 showing that donor IL-17-producing cells ameliorated acute GVHD. Host DCs are critical in the initiation of acute GVHD, [52][53][54] leading to a hypothesis that IL-17-producing cells could modify the function of host DCs through unknown mechanisms. Direct interaction between IL-17 and host DCs may be supported by the fact that DCs expressed IL-17 receptors.…”

Section: Discussionmentioning

confidence: 99%

A single nucleotide polymorphism of IL-17 gene in the recipient is associated with acute GVHD after HLA-matched unrelated BMT

Espinoza

Takami

Onizuka

et al. 2011

Bone Marrow Transplant

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IL-17 has an important role in the host defense against extracellular pathogens and the pathophysiology of autoimmune diseases. This study retrospectively examined the impact of a single-nucleotide polymorphism (rs2275913, G197A) in the IL-17 gene of a total 510 recipients with hematologic malignancies and their unrelated donors on the clinical outcomes in HLAmatched myeloablative (discovery study) and nonmyeloablative (validation study) BMT through the Japan Marrow Donor Program (JMDP). In the discovery study, the presence of a 197A genotype in the recipient resulted in a higher incidence of grades II-IV acute GVHD (hazard ratio (HR), 1.87; 95% confidence interval (CI), 1.23-2.85; P ¼ 0.004). The donor IL-17A genotype did not significantly influence the transplant outcomes. The validation study showed a trend toward an association of the recipient 197A genotype with an increased risk of grades III-IV acute GVHD (HR, 5.84; 95% CI,; P ¼ 0.09), as well as a significantly increased risk for chronic GVHD (HR, 3.86; 95% CI, 1.29-11.59; P ¼ 0.02). These results suggest an association of the 197A genotype in the recipient side with the development of acute GVHD.

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Section: Discussionmentioning

confidence: 99%

A single nucleotide polymorphism of IL-17 gene in the recipient is associated with acute GVHD after HLA-matched unrelated BMT

Espinoza

Takami

Onizuka

et al. 2011

Bone Marrow Transplant

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“…For the same reason reduced intensity conditioning causes less aGVHD as there is decreased damage from the conditioning regimen to the host tissue leading to less activation of the immune cascade [24,25]. In nonclinical models GVHD can be reduced via manipulation of APCs as well [26,27]. Also non-hematopoietic cells such as mesenchymal stromal cells have been shown to decrease the activity of alloreactive T cells leading to reduced GVHD although the mechanism of such interaction is poorly understood at this time [28].…”

Section: Pathophysiologymentioning

confidence: 99%

State-of-the-art acute and chronic GVHD treatment

Jamil

Mineishi

2015

Int J Hematol

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owing to the advancement in reduced intensity conditioning (RIC) and in patients without HLA-matched donors due to the use of cord blood and haploidentical HSCT [4][5][6]. Although marked improvement has been made in supportive care, immunosuppressive therapy and DNA-based Human Leukocyte Antigen (HLA) typing, graft vs host disease (GVHD) remains a major cause of morbidity and non-relapse mortality among allogeneic HSCT recipients. It was first described by Billingham in 1966 as a syndrome where immunocompetent T cells from the donor recognize and damage the host tissue in an immunocompromised recipient. It presents with heterogeneous symptoms involving multiple organ systems including gastrointestinal tract, skin, mucosa, liver and lungs [7]. In the past clinical features occurring within 100 days after HSCT was called acute GVHD (aGVHD) and those happening after 100 days were labeled chronic GVHD (cGVHD) [8,9]. This definition was rather unsatisfactory thus National Institute of Health (NIH) consensus criteria were developed and have been revised. The criteria have added new categories such as late-onset aGVHD (acute GVHD occurring after 100 days) and overlap syndrome which includes features of both acute and chronic GVHD to the classification, and also have introduced new definitions for organ system involvement [10][11][12]. The categorization of acute vs chronic GVHD is based on the combination of clinical symptoms rather than the time of onset. Depending upon a number of variables associated with patients, donors, and types of transplant, the incidence of aGVHD varies with incidence of grade II-IV GVHD at 40 % in matched related donor (MRD) transplant to 50 % in MUD transplant. The main risk factors for aGVHD include degree of HLA mismatch, age of the patient, previous all immunization of the donor and the kind of GVHD prophylaxis used. About 30-70 % of allogeneic HSCT recipients alive after 100 days will Abstract Graft-versus-host disease (GVHD) remains as the major obstacle for successful hematopoietic stem cell transplant (HSCT). Roughly half of the patients undergoing HSCT develop GVHD which requires treatment, and above 10 % of the patient may die because of it. However, GVHD presents with anti-tumor activity, called graft-versus-tumor (GVT) effect, and it carries significant anti-tumor activity, thus suppressing GVHD completely may increase the relapse of original disease. Thus, it is important to control GVHD to the appropriate level.

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“…5 To mount an efficient alloresponse, antigens need to be presented by professional antigen presenting cells (APCs) with host APCs being crucial for the initiation of GVHD. [6][7][8][9][10] Depletion of APCs in the liver and the spleen significantly inhibits the recruitment and proliferation of donor T cells, 11 and the elimination of Langerhans cells seems to be efficient in preventing skin GVHD. 12 However, there is also increasing evidence implicating crosspresenting donor APCs in acute 13 and chronic 14 GVHD.…”

Section: Introductionmentioning

confidence: 99%