Matches in SemOpenAlex for { <https://semopenalex.org/work/W3017388612> ?p ?o ?g. }
- W3017388612 abstract "The human T lymphocyte compartment is highly dynamic over the course of a lifetime. Of the many changes, perhaps most notable is the transition from a predominantly naïve T cell state at birth to the acquisition of antigen-experienced memory and effector subsets following environmental exposures. These phenotypic changes, including the induction of T cell exhaustion and senescence, have the potential to negatively impact efficacy of adoptive T cell therapies (ACT). When considering ACT with CD4+CD25+CD127-/lo regulatory T cells (Tregs) for the induction of immune tolerance, we previously reported ex vivo expanded umbilical cord blood (CB) Tregs remained more naïve, suppressed responder T cells equivalently, and exhibited a more diverse T cell receptor (TCR) repertoire compared to expanded adult peripheral blood (APB) Tregs. Herein, we hypothesized that upon further characterization, we would observe increased lineage heterogeneity and phenotypic diversity in APB Tregs that might negatively impact lineage stability, engraftment capacity, and the potential for Tregs to home to sites of tissue inflammation following ACT. We compared the phenotypic profiles of human Tregs isolated from CB versus the more traditional source, APB. We conducted analysis of fresh and ex vivo expanded Treg subsets at both the single cell (scRNA-seq and flow cytometry) and bulk (microarray and cytokine profiling) levels. Single cell transcriptional profiles of pre-expansion APB Tregs highlighted a cluster of cells that showed increased expression of genes associated with effector and pro-inflammatory phenotypes (CCL5, GZMK, BHLHE40, CXCR3, and LYAR) with low expression of Treg markers (FOXP3 and IKZF2). CB Tregs were more diverse in TCR repertoire and homogenous in phenotype, and contained fewer effector-like cells in contrast with APB Tregs. Interestingly, expression of canonical Treg markers, such as FOXP3, TIGIT and IKZF2, were increased in CB CD4+CD127+ conventional T cells (Tconv) compared to APB Tconv, post-expansion, implying perinatal T cells may adopt a default regulatory program. Collectively, these data identify multiple surface markers (CXCR3, CCL5, and NKG7) that could be depleted to improve purity and stability of APB Tregs, and support the use of expanded CB Tregs as a potentially optimal ACT modality for the treatment of autoimmune and inflammatory diseases." @default.
- W3017388612 created "2020-04-24" @default.
- W3017388612 creator A5000610987 @default.
- W3017388612 creator A5011141535 @default.
- W3017388612 creator A5011277486 @default.
- W3017388612 creator A5013112733 @default.
- W3017388612 creator A5015872241 @default.
- W3017388612 creator A5017740692 @default.
- W3017388612 creator A5022970292 @default.
- W3017388612 creator A5046845352 @default.
- W3017388612 creator A5047782710 @default.
- W3017388612 creator A5052802925 @default.
- W3017388612 creator A5057502799 @default.
- W3017388612 creator A5064971080 @default.
- W3017388612 creator A5088031712 @default.
- W3017388612 date "2020-04-15" @default.
- W3017388612 modified "2023-10-15" @default.
- W3017388612 title "Human Regulatory T Cells From Umbilical Cord Blood Display Increased Repertoire Diversity and Lineage Stability Relative to Adult Peripheral Blood" @default.
- W3017388612 cites W1483854882 @default.
- W3017388612 cites W1523413731 @default.
- W3017388612 cites W1641463952 @default.
- W3017388612 cites W1652175895 @default.
- W3017388612 cites W1678352491 @default.
- W3017388612 cites W1777296950 @default.
- W3017388612 cites W1903263117 @default.
- W3017388612 cites W1935040042 @default.
- W3017388612 cites W1951724000 @default.
- W3017388612 cites W1972263413 @default.
- W3017388612 cites W1982425127 @default.
- W3017388612 cites W1986935294 @default.
- W3017388612 cites W1989025715 @default.
- W3017388612 cites W1991748190 @default.
- W3017388612 cites W1992776047 @default.
- W3017388612 cites W2001809800 @default.
- W3017388612 cites W2004607223 @default.
- W3017388612 cites W2007631222 @default.
- W3017388612 cites W2009253992 @default.
- W3017388612 cites W2015002525 @default.
- W3017388612 cites W2015280752 @default.
- W3017388612 cites W2015990121 @default.
- W3017388612 cites W2024691638 @default.
- W3017388612 cites W2035606942 @default.
- W3017388612 cites W2035855795 @default.
- W3017388612 cites W2036732971 @default.
- W3017388612 cites W2041390189 @default.
- W3017388612 cites W2046442721 @default.
- W3017388612 cites W2054738595 @default.
- W3017388612 cites W2065045458 @default.
- W3017388612 cites W2065434799 @default.
- W3017388612 cites W2075326117 @default.
- W3017388612 cites W2077096670 @default.
- W3017388612 cites W2079312631 @default.
- W3017388612 cites W2080935386 @default.
- W3017388612 cites W2084317828 @default.
- W3017388612 cites W2087985268 @default.
- W3017388612 cites W2093324837 @default.
- W3017388612 cites W2094788591 @default.
- W3017388612 cites W2098972497 @default.
- W3017388612 cites W2099570622 @default.
- W3017388612 cites W2101449057 @default.
- W3017388612 cites W2105484520 @default.
- W3017388612 cites W2106837070 @default.
- W3017388612 cites W2109611466 @default.
- W3017388612 cites W2109846062 @default.
- W3017388612 cites W2110006696 @default.
- W3017388612 cites W2114173006 @default.
- W3017388612 cites W2118209956 @default.
- W3017388612 cites W2119896120 @default.
- W3017388612 cites W2119991694 @default.
- W3017388612 cites W2122091248 @default.
- W3017388612 cites W2123612933 @default.
- W3017388612 cites W2128120736 @default.
- W3017388612 cites W2129292145 @default.
- W3017388612 cites W2129741568 @default.
- W3017388612 cites W2134907948 @default.
- W3017388612 cites W2136245823 @default.
- W3017388612 cites W2140457680 @default.
- W3017388612 cites W2144843164 @default.
- W3017388612 cites W2145217698 @default.
- W3017388612 cites W2145985838 @default.
- W3017388612 cites W2146512944 @default.
- W3017388612 cites W2147172932 @default.
- W3017388612 cites W2147953838 @default.
- W3017388612 cites W2149209349 @default.
- W3017388612 cites W2150145041 @default.
- W3017388612 cites W2150644622 @default.
- W3017388612 cites W2150901150 @default.
- W3017388612 cites W2152642587 @default.
- W3017388612 cites W2152759011 @default.
- W3017388612 cites W2156964052 @default.
- W3017388612 cites W2159514218 @default.
- W3017388612 cites W2160700813 @default.
- W3017388612 cites W2162666968 @default.
- W3017388612 cites W2164857852 @default.
- W3017388612 cites W2164872587 @default.
- W3017388612 cites W2165204759 @default.
- W3017388612 cites W2169456326 @default.
- W3017388612 cites W2169800587 @default.
- W3017388612 cites W2188074886 @default.
- W3017388612 cites W2195684699 @default.