ArticleGut2016
Developing in vitro expanded CD45RA+ regulatory T cells as an adoptive cell therapy for Crohn's disease.
Article in Gut, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03185000 (A First in Human Feasibility Study of T Regulatory Cells), which is not on this map. Cited by 122 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A First in Human Feasibility Study of T Regulatory Cells (TR004) for Inflammatory Bowel Disease Using (ex Vivo) Treg Expansion
Who cites it
122 citing papers in PubMed, 2 syntheses or guidelines pooled it, 192 citations in OpenAlex.
- Emerging CAR-Treg and regulatory T cell therapies for inflammatory bowel diseases: a systematic review of a new era of treatment.Frontiers in immunology · 2026Pooled it
- Engineered antigen-specific regulatory T cells for autoimmune skin conditions.Autoimmunity reviews · 2021Pooled it
- From technological iteration to clinical breakthrough: advances of CAR-T cell therapy in autoimmune diseases.Annals of medicine · 2026Review
- Engineering immune cell therapies for inflammatory bowel disease: from stem cells to CAR T cells.Nature reviews. Gastroenterology & hepatology · 2026Review
- Review
- Next-Generation regulatory T cell therapies: Translational considerations for inflammatory bowel disease.Human immunology · 2026Review
- Are All Cells Created Equal? Novel Cell-Based Regenerative Therapies in Inflammatory Bowel Disease.International journal of molecular sciences · 2026Review
- Isolation of Pure Stable Human Treg Cells Based on Expression of GPA33.European journal of immunology · 2026Article
- Intestinal transcriptomic analysis and prediction of biomarkers associated with mucosal healing following vedolizumab treatment in ulcerative colitis using machine learning.BMC gastroenterology · 2026Article
- Delineating phenotypic heterogeneity in human regulatory T cells across developmental stages and therapeutic sources.Frontiers in immunology · 2026Article
- Gut microbiota in regulatory T cell generation and function: mechanisms and health implications.Gut microbes · 2025Review
- Human precursor T follicular regulatory cells are primed for differentiation into mature Tfr and disrupted during severe infections.Science advances · 2025Article
- Nanoneedle-Based Electroporation for Efficient Manufacturing of Human Primary Chimeric Antigen Receptor Regulatory T-Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Initial or continuous coculture with umbilical cord-derived mesenchymal stromal cells facilitates in vitro expansion of human regulatory T-cell subpopulations.Stem cells translational medicine · 2025Article
- Second generation CD2-targeting LFA-3 fusion protein SBT115301 to restore immune homeostasis in autoimmune disease.iScience · 2025Article
- Article
- IL23R-Specific CAR Tregs for the Treatment of Crohn's Disease.Journal of Crohn's & colitis · 2025Article
- Article
- Navigating the manufacturing, testing and regulatory complexities of regulatory T cells for adoptive cell therapy.Frontiers in immunology · 2025Review
- Article
62 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 9 institutions in 2 countries.
Funding
Abstract
BACKGROUND AND
aimThymus-derived regulatory T cells (Tregs) mediate dominant peripheral tolerance and treat experimental colitis. Tregs can be expanded from patient blood and were safely used in recent phase 1 studies in graft versus host disease and type 1 diabetes. Treg cell therapy is also conceptually attractive for Crohn's disease (CD). However, barriers exist to this approach. The stability of Tregs expanded from Crohn's blood is unknown. The potential for adoptively transferred Tregs to express interleukin-17 and exacerbate Crohn's lesions is of concern. Mucosal T cells are resistant to Treg-mediated suppression in active CD. The capacity for expanded Tregs to home to gut and lymphoid tissue is unknown.
methodsTo define the optimum population for Treg cell therapy in CD, CD4(+)CD25(+)CD127(lo)CD45RA(+) and CD4(+)CD25(+)CD127(lo)CD45RA(-) Treg subsets were isolated from patients' blood and expanded in vitro using a workflow that can be readily transferred to a good manufacturing practice background.
resultsTregs can be expanded from the blood of patients with CD to potential target dose within 22-24 days. Expanded CD45RA(+) Tregs have an epigenetically stable FOXP3 locus and do not convert to a Th17 phenotype in vitro, in contrast to CD45RA(-) Tregs. CD45RA(+) Tregs highly express α4β7 integrin, CD62L and CC motif receptor 7 (CCR7). CD45RA(+) Tregs also home to human small bowel in a C.B-17 severe combined immune deficiency (SCID) xenotransplant model. Importantly, in vitro expansion enhances the suppressive ability of CD45RA(+) Tregs. These cells also suppress activation of lamina propria and mesenteric lymph node lymphocytes isolated from inflamed Crohn's mucosa.
conclusionsCD4(+)CD25(+)CD127(lo)CD45RA(+) Tregs may be the most appropriate population from which to expand Tregs for autologous Treg therapy for CD, paving the way for future clinical trials.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.