FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2807569520> ?p ?o ?g. }

• W2807569520 abstract "Immunosuppressive drugs have facilitated the progression of solid organ transplantation from experimental therapy to routine practice, however transplant recipients are still susceptible to chronic rejection and co-morbidities. The emergence of regulatory T cells (Treg) as a key regulator of the immune system, together with an abundance of evidence from experimental transplant models, has led to clinical trials asking whether Treg can improve transplant outcomes. However, given that Treg cellular therapy will only be acceptable if introduced into current immunosuppressive regimens, a critical question is how Treg will respond in the presence of concomitant immunosuppression. Whilst in vitro data are available, very few credible experiments have been done asking whether individual immunosuppressive drugs have a positive, a neutral or a detrimental impact on the Treg function in vivo . Thus the aims of this thesis were firstly to generate sufficient numbers of adaptive Treg for extensive experimental use and secondly to evaluate their ability to control transplant rejection in vivo in the presence of biologically valid doses of individual, clinically relevant immunosuppressive drugs. Importantly, the model chosen was the heterotopic heart transplant model in lymphoreplete mice to avoid possible artefacts that can occur in cell reconstituted lympho-depleted mice. The model also has the added advantage that by dealing with an intact immune system, it perhaps represents a small step closer to the clinical situation. Generating sufficient numbers of stable Treg was necessary for planned in vivo experiments. Incubating CD4+ T cells with anti-CD44 antibody, prior to driving them with bone-marrow derived dendritic cells, enriched for a stable population of Treg and importantly yielded sufficient numbers of cells for in vivo experiments. It is frequently stated that alloantigen-driven Treg are more efficacious than activated autologous nTreg, however there was no difference in rejection kinetics in either a skin or heart allograft model when comparing alloantigen-driven Treg with nTreg. As generating alloantigen-driven Treg is less efficient than nTreg, pursuing the former as a potential therapy might therefore be unnecessary. This could have a considerable impact on the logistics and the practicality of clinical Treg cellular therapeutics. The timing of Treg administration is an important consideration to maximise efficacy. Pre-transplant administration led to the longest graft survival times, suggesting that this is the most effective time for cell delivery. Preclinical models provide a useful tool to ask how immunosuppressive drugs will affect adoptively transferred Treg. The data presented in this thesis suggest that combining Treg with Rapamycin, Mycophenolate Mofetil (MMF) or Tacrolimus did not completely prevent Treg function. However, Methylprednisolone (MP) did prevent Treg function, suggesting it cannot be used with adoptively transferred Treg. Overall, these results provide important data for the design of immunosuppressive regimens for future clinical trials assessing the efficacy of Treg in transplant recipients." @default.
• W2807569520 created "2018-06-13" @default.
• W2807569520 creator A5040332811 @default.
• W2807569520 date "2016-01-01" @default.
• W2807569520 modified "2023-09-27" @default.
• W2807569520 title "Assessing the impact of immunosuppressive drugs on regulatory T cell therapy" @default.
• W2807569520 hasPublicationYear "2016" @default.
• W2807569520 type Work @default.
• W2807569520 sameAs 2807569520 @default.
• W2807569520 citedByCount "0" @default.
• W2807569520 crossrefType "dissertation" @default.
• W2807569520 hasAuthorship W2807569520A5040332811 @default.
• W2807569520 hasConcept C126322002 @default.
• W2807569520 hasConcept C150903083 @default.
• W2807569520 hasConcept C168444539 @default.
• W2807569520 hasConcept C203014093 @default.
• W2807569520 hasConcept C207001950 @default.
• W2807569520 hasConcept C2776090121 @default.
• W2807569520 hasConcept C2778296632 @default.
• W2807569520 hasConcept C2778330430 @default.
• W2807569520 hasConcept C2780179540 @default.
• W2807569520 hasConcept C2780252810 @default.
• W2807569520 hasConcept C2911091166 @default.
• W2807569520 hasConcept C71924100 @default.
• W2807569520 hasConcept C79484868 @default.
• W2807569520 hasConcept C86803240 @default.
• W2807569520 hasConcept C8891405 @default.
• W2807569520 hasConceptScore W2807569520C126322002 @default.
• W2807569520 hasConceptScore W2807569520C150903083 @default.
• W2807569520 hasConceptScore W2807569520C168444539 @default.
• W2807569520 hasConceptScore W2807569520C203014093 @default.
• W2807569520 hasConceptScore W2807569520C207001950 @default.
• W2807569520 hasConceptScore W2807569520C2776090121 @default.
• W2807569520 hasConceptScore W2807569520C2778296632 @default.
• W2807569520 hasConceptScore W2807569520C2778330430 @default.
• W2807569520 hasConceptScore W2807569520C2780179540 @default.
• W2807569520 hasConceptScore W2807569520C2780252810 @default.
• W2807569520 hasConceptScore W2807569520C2911091166 @default.
• W2807569520 hasConceptScore W2807569520C71924100 @default.
• W2807569520 hasConceptScore W2807569520C79484868 @default.
• W2807569520 hasConceptScore W2807569520C86803240 @default.
• W2807569520 hasConceptScore W2807569520C8891405 @default.
• W2807569520 hasLocation W28075695201 @default.
• W2807569520 hasOpenAccess W2807569520 @default.
• W2807569520 hasPrimaryLocation W28075695201 @default.
• W2807569520 hasRelatedWork W1554901867 @default.
• W2807569520 hasRelatedWork W18916504 @default.
• W2807569520 hasRelatedWork W2013707249 @default.
• W2807569520 hasRelatedWork W2037330132 @default.
• W2807569520 hasRelatedWork W2095378498 @default.
• W2807569520 hasRelatedWork W2165923734 @default.
• W2807569520 hasRelatedWork W2243664192 @default.
• W2807569520 hasRelatedWork W2308700479 @default.
• W2807569520 hasRelatedWork W2416241390 @default.
• W2807569520 hasRelatedWork W2564221293 @default.
• W2807569520 hasRelatedWork W2765413797 @default.
• W2807569520 hasRelatedWork W2801024566 @default.
• W2807569520 hasRelatedWork W2909656857 @default.
• W2807569520 hasRelatedWork W3143685804 @default.
• W2807569520 hasRelatedWork W3173823183 @default.
• W2807569520 hasRelatedWork W3200040940 @default.
• W2807569520 hasRelatedWork W3207425110 @default.
• W2807569520 hasRelatedWork W931669152 @default.
• W2807569520 hasRelatedWork W2308426633 @default.
• W2807569520 hasRelatedWork W2926551739 @default.
• W2807569520 isParatext "false" @default.
• W2807569520 isRetracted "false" @default.
• W2807569520 magId "2807569520" @default.
• W2807569520 workType "dissertation" @default.