FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2554458459> ?p ?o ?g. }

• W2554458459 abstract "Abstract Abstract 3746 Acute graft-versus-host disease (aGvHD) is an immune syndrome after allogeneic hematopoietic cell transplantation (allo-HCT) caused by alloreactive donor T cells that attack the gastrointestinal tract, liver and skin. Thus, early T cell migration patterns to these organs could provide first cues for the onset of aGvHD. Hence, a unique surface marker profile of donor T cells at early time points after allo-HCT may be an indicator for patients at risk of aGVHD. Therefore, we analyzed the course of donor T cell activation, proliferation and homing in a clinical relevant murine MHC minor mismatch (miHAg) allo-HCT model to define critical time points and marker profiles for the detection of alloreactive T cells. Luciferase-labeled C57Bl/6 (H-2b) T cells plus bone marrow cells were transplanted into conditioned (8 Gy) MHC major mismatched Balb/c (H-2d) or miHAg Balb/b (H-2b) recipients. Donor T cell migration was visualized by in vivo bioluminescence imaging (BLI) and cells were characterized by multiparameter flow cytometry for 30 consecutive days after allo-HCT. GVHD scoring was performed by histopathology. Donor T cells proliferated exclusively in secondary lymphoid organs until day+3 (initiation phase) before migrating via the peripheral blood into target organs (effector phase). This occured in both models, MHC major mismatch and miHAg allo-HCT, which resulted in hyper-acute (starting at day+6) or acute GVHD (starting at day+21), respectively. In the hyper-acute scenario one wave of T cell migration starting at day+4 sufficed to cause lethal aGVHD. We detected a 4000-fold increase in CD4 and a 1500-fold increase in CD8 donor T cell numbers in the peripheral blood between day+3 and day+6 in this model. In contrast, in the more clinical relevant miHAg allo-HCT model we found 3 waves of T cell migration with peaks at days +6, +11 and +15 after allo-HCT. In the peripheral blood CD4 T cells increased 20-fold, CD8 T cells 50-fold between day+3 and day+6, but more than 40-fold (CD4) and 400-fold (CD8) between day+3 and day+11. After the third peak on day+15 a period followed when we could only detect very few migrating donor T cells in the peripheral blood before aGvHD became clinically apparent on day+21. Next, we asked whether we could identify alloreactive T cells by testing a large panel of surface markers at the defined migration peaks. Indeed, allogeneic T cells upregulated certain homing receptors at these peaks (e.g. at day+11: α4β7 integrin: 27% of CD4 T cells, 3.4×104/ml, 60% of CD8 T cells, 1.6×105/ml; P-selectin ligand: 28% of CD4 T cells, 3.5×104/ml, 35% of CD8 T cells, 9.1×104/ml). In contrast, syngeneic transplanted mice only showed a constant low expression level of those receptors (e.g. at day+11: α4β7 integrin: 20% of CD4 T cells, 9.6×103/ml, 5% of CD8 T cells, 3.1×103/ml; P-selectin ligand: 17% of CD4 T cells, 8.5×103/ml, 10% of CD8 T cells, 6.6×103/ml). However, other markers such as CD44 could be found on more than 80% of all donor T cells in allogeneic or syngeneic recipients. Our results in this clinical relevant mouse model show accelerating waves of T cell migration consistent with an enhancing feedback loop model of aGvHD pathogenesis. The homing receptor expression profile of donor T cells correlated with critical migration waves and clearly differed between mice with or without aGvHD. The assessment of critical time points frame a diagnostic window for a potential predictive test based on the dynamic change of the T cell homing receptor profile after allo-HCT. This preclinical study now awaits to be evaluated in patients undergoing allo-HCT. Disclosures: No relevant conflicts of interest to declare." @default.
• W2554458459 created "2016-11-30" @default.
• W2554458459 creator A5005492422 @default.
• W2554458459 creator A5016360607 @default.
• W2554458459 creator A5026165158 @default.
• W2554458459 creator A5030429968 @default.
• W2554458459 creator A5050924642 @default.
• W2554458459 creator A5064976360 @default.
• W2554458459 creator A5069434242 @default.
• W2554458459 creator A5079647703 @default.
• W2554458459 creator A5080071989 @default.
• W2554458459 creator A5085514827 @default.
• W2554458459 creator A5085953142 @default.
• W2554458459 creator A5090367243 @default.
• W2554458459 creator A5030305055 @default.
• W2554458459 date "2010-11-19" @default.
• W2554458459 modified "2023-09-30" @default.
• W2554458459 title "Definition of a Diagnostic Window Prior to the Onset of Clinically Apparent Acute Graft-Versus-Host Disease." @default.
• W2554458459 doi "https://doi.org/10.1182/blood.v116.21.3746.3746" @default.
• W2554458459 hasPublicationYear "2010" @default.
• W2554458459 type Work @default.
• W2554458459 sameAs 2554458459 @default.
• W2554458459 citedByCount "0" @default.
• W2554458459 crossrefType "journal-article" @default.
• W2554458459 hasAuthorship W2554458459A5005492422 @default.
• W2554458459 hasAuthorship W2554458459A5016360607 @default.
• W2554458459 hasAuthorship W2554458459A5026165158 @default.
• W2554458459 hasAuthorship W2554458459A5030305055 @default.
• W2554458459 hasAuthorship W2554458459A5030429968 @default.
• W2554458459 hasAuthorship W2554458459A5050924642 @default.
• W2554458459 hasAuthorship W2554458459A5064976360 @default.
• W2554458459 hasAuthorship W2554458459A5069434242 @default.
• W2554458459 hasAuthorship W2554458459A5079647703 @default.
• W2554458459 hasAuthorship W2554458459A5080071989 @default.
• W2554458459 hasAuthorship W2554458459A5085514827 @default.
• W2554458459 hasAuthorship W2554458459A5085953142 @default.
• W2554458459 hasAuthorship W2554458459A5090367243 @default.
• W2554458459 hasConcept C109159458 @default.
• W2554458459 hasConcept C111335760 @default.
• W2554458459 hasConcept C126322002 @default.
• W2554458459 hasConcept C151872237 @default.
• W2554458459 hasConcept C161997846 @default.
• W2554458459 hasConcept C18903297 @default.
• W2554458459 hasConcept C203014093 @default.
• W2554458459 hasConcept C2776090121 @default.
• W2554458459 hasConcept C2779972918 @default.
• W2554458459 hasConcept C2780007613 @default.
• W2554458459 hasConcept C28328180 @default.
• W2554458459 hasConcept C2911091166 @default.
• W2554458459 hasConcept C54009773 @default.
• W2554458459 hasConcept C54355233 @default.
• W2554458459 hasConcept C71924100 @default.
• W2554458459 hasConcept C81885089 @default.
• W2554458459 hasConcept C86803240 @default.
• W2554458459 hasConcept C8891405 @default.
• W2554458459 hasConceptScore W2554458459C109159458 @default.
• W2554458459 hasConceptScore W2554458459C111335760 @default.
• W2554458459 hasConceptScore W2554458459C126322002 @default.
• W2554458459 hasConceptScore W2554458459C151872237 @default.
• W2554458459 hasConceptScore W2554458459C161997846 @default.
• W2554458459 hasConceptScore W2554458459C18903297 @default.
• W2554458459 hasConceptScore W2554458459C203014093 @default.
• W2554458459 hasConceptScore W2554458459C2776090121 @default.
• W2554458459 hasConceptScore W2554458459C2779972918 @default.
• W2554458459 hasConceptScore W2554458459C2780007613 @default.
• W2554458459 hasConceptScore W2554458459C28328180 @default.
• W2554458459 hasConceptScore W2554458459C2911091166 @default.
• W2554458459 hasConceptScore W2554458459C54009773 @default.
• W2554458459 hasConceptScore W2554458459C54355233 @default.
• W2554458459 hasConceptScore W2554458459C71924100 @default.
• W2554458459 hasConceptScore W2554458459C81885089 @default.
• W2554458459 hasConceptScore W2554458459C86803240 @default.
• W2554458459 hasConceptScore W2554458459C8891405 @default.
• W2554458459 hasLocation W25544584591 @default.
• W2554458459 hasOpenAccess W2554458459 @default.
• W2554458459 hasPrimaryLocation W25544584591 @default.
• W2554458459 hasRelatedWork W1910899214 @default.
• W2554458459 hasRelatedWork W2042877290 @default.
• W2554458459 hasRelatedWork W2066889665 @default.
• W2554458459 hasRelatedWork W2158573399 @default.
• W2554458459 hasRelatedWork W2181013172 @default.
• W2554458459 hasRelatedWork W2354018035 @default.
• W2554458459 hasRelatedWork W2367923750 @default.
• W2554458459 hasRelatedWork W2384268593 @default.
• W2554458459 hasRelatedWork W2387899401 @default.
• W2554458459 hasRelatedWork W2390830377 @default.
• W2554458459 hasRelatedWork W2535136043 @default.
• W2554458459 hasRelatedWork W2549969674 @default.
• W2554458459 hasRelatedWork W2553394890 @default.
• W2554458459 hasRelatedWork W2563412259 @default.
• W2554458459 hasRelatedWork W2567336100 @default.
• W2554458459 hasRelatedWork W2571432015 @default.
• W2554458459 hasRelatedWork W2908969860 @default.
• W2554458459 hasRelatedWork W2994011911 @default.
• W2554458459 hasRelatedWork W82106091 @default.
• W2554458459 hasRelatedWork W95320356 @default.
• W2554458459 isParatext "false" @default.
• W2554458459 isRetracted "false" @default.
• W2554458459 magId "2554458459" @default.
• W2554458459 workType "article" @default.