About: Human LAP(+)GARP(+)FOXP3(+) regulatory T cells attenuate xenogeneic graft versus host disease

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About: Human LAP(+)GARP(+)FOXP3(+) regulatory T cells attenuate xenogeneic graft versus host disease Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Human LAP(+)GARP(+)FOXP3(+) regulatory T cells attenuate xenogeneic graft versus host disease
Creator	Tran, Dat Cooper, Laurence Olek, Sven Pham, Anha Schulze, Janika Song, Hyo Wang, Huihui
Source	PMC
abstract	Adoptive transfer of regulatory T cells (FOXP3(+) Tregs) has been developed as a potential curative immune therapy to prevent and treat autoimmune and graft-versus-host diseases (GVHD). A major limitation that has hindered the use of Treg immunotherapy in humans is the difficulty of consistently isolating and obtaining highly purified Tregs after ex vivo expansion. Methods: We isolated bona fide Tregs from expansion cultures based on their selective surface expression of latency-associated peptide (LAP). The TCR Vβ diversity and intracellular cytokine production of Tregs were determined by flow cytometer. The TSDR methylation was determined by epigenetic human FOXP3 qPCR Assay. Their in vitro and in vivo potency was confirmed with suppression assay and humanized xenogeneic GVHD (xGVHD) murine model, respectively. Results: LAP(+) repurification results in >90% LAP(+)FOXP3(+) Tregs, leaving behind FOXP3(-) and FOXP3(+) nonTregs within the LAP(-) population. After 4-week expansion, the LAP(+) Tregs were >1 billion cells, highly suppressive and anergic in vitro, >90% demethylated in the TSDR and able to maintain TCR Vβ diversity. In the xGVHD model, exogenous CD25(-)PBMC administered alone results in a median survival of 32 days. The co-transfer of LAP(+) Tregs increased median survival to 47 days, while the LAP parent (CD25(+)) and LAP(-) nonTregs had median survival of 39 and 31 days, respectively. Conclusions: These preclinical data together provide evidence that LAP(+) Tregs are highly purified with fully suppressive function for cell therapy. This population results in a more effective and safer product for immunotherapy to treat GVHD and provides the necessary preclinical data for transition into a clinical trial with LAP(+) Tregs to prevent or treat GVHD and other autoimmune diseases.
has issue date	2019-04-12(xsd:dateTime)
bibo:doi	10.7150/thno.30254
bibo:pmid	31149046
has license	cc-by-nc
sha1sum (hex)	13b16688b86661a6165f9c688c4f45893b7e47c5
schema:url	https://doi.org/10.7150/thno.30254
resource representing a document's title	Human LAP(+)GARP(+)FOXP3(+) regulatory T cells attenuate xenogeneic graft versus host disease
has PubMed Central identifier	PMC6531299
has PubMed identifier	31149046
schema:publication	Theranostics
resource representing a document's body	covid:13b16688b86661a6165f9c688c4f45893b7e47c5#body_text
is schema:about of	named entity 'GARP' named entity 'ATTENUATE' named entity 'DIFFICULTY' named entity 'EXPANSION' named entity 'SURFACE' named entity 'BASED' named entity 'TRANSITION' named entity 'REGULATORY T CELLS' named entity 'IMMUNOTHERAPY' named entity 'HUMAN' named entity 'MURINE' named entity 'SELECTIVE' named entity 'ADOPTIVE TRANSFER' named entity 'ISOLATED' named entity 'CLINICAL TRIAL' named entity 'SUPPRESSION' named entity 'A MAJOR' named entity 'NECESSARY' named entity 'FULLY' named entity 'ADMINISTERED' named entity 'TO PREVENT' named entity 'GVHD' named entity 'ISOLATING' named entity 'EXOGENOUS' named entity 'DIVERSITY' named entity 'CONCLUSIONS' named entity 'FUNCTION' named entity '3E1' named entity 'SURVIVAL' named entity 'LATENCY-ASSOCIATED PEPTIDE' named entity 'CD25' named entity 'survival' named entity 'intracellular' named entity 'FOXP3' named entity 'qPCR' named entity 'Tregs' named entity 'regulatory T cells' named entity 'vivo' named entity 'leaving' named entity 'xenogeneic' named entity 'Human' named entity 'HUMAN' covid:arg/13b16688b86661a6165f9c688c4f45893b7e47c5 named entity 'GRAFT VERSUS HOST DISEASE' named entity 'EXPRESSION' named entity 'HUMANS' named entity 'PBMC' named entity 'EPIGENETIC' named entity 'METHODS' named entity 'TREAT' named entity 'INCREASED' named entity 'THESE' named entity 'ASSAY' named entity 'HUMANIZED' named entity 'TCR' named entity 'AUTOIMMUNE DISEASES' named entity 'USE OF' named entity 'EVIDENCE' named entity 'FOXP3' named entity 'IN VITRO' named entity 'LEAVING' named entity 'THEIR' named entity 'DAYS' named entity 'TO MAINTAIN' named entity 'DATA' named entity 'MEDIAN' named entity 'HIGHLY' named entity 'PRODUCT' named entity 'CELL THERAPY' named entity 'QPCR ASSAY' named entity 'SUPPRESSIVE' named entity 'CURATIVE' named entity 'INTRACELLULAR' named entity 'LIMITATION' named entity 'FOXP3'

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