ArticleBiology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation2011
Alloreactivity across HLA barriers is mediated by both naïve and antigen-experienced T cells.
Article in Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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.
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Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- Ultra low-dose IL-2 for GVHD prophylaxis after allogeneic hematopoietic stem cell transplantation mediates expansion of regulatory T cells without diminishing antiviral and antileukemic activity.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Trial
- Intrinsic tumor cell line immunogenicity may drive CAR-independent T cell responses and confound CAR T cell preclinical modeling.Journal for immunotherapy of cancer · 2026Article
- Evaluation of multi-antigen targeting ADCC strategies in pediatric BCP-ALL.Journal for immunotherapy of cancer · 2025Article
- Alloreactive memory CD4 T cells promote transplant rejection by engaging DCs to induce innate inflammation and CD8 T cell priming.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Virus-Specific T-Cell Therapy for Viral Infections of the Central Nervous System: A Review.Viruses · 2023Review
- Article
- High Throughput Human T Cell Receptor Sequencing: A New Window Into Repertoire Establishment and Alloreactivity.Frontiers in immunology · 2021Review
- Donor-derived CD4Bone marrow transplantation · 2019Article
- Low-dose donor memory T-cell infusion after TCR alpha/beta depleted unrelated and haploidentical transplantation: results of a pilot trial.Bone marrow transplantation · 2018Article
- Cytomegalovirus induces HLA-class-II-restricted alloreactivity in an acute myeloid leukemia cell line.PloS one · 2018Article
- Graft versus tumor effects and why people relapse.Hematology. American Society of Hematology. Education Program · 2017Review
- HLA-DP in unrelated hematopoietic cell transplantation revisited: challenges and opportunities.Blood · 2017Review
- Adenosine Selectively Depletes Alloreactive T Cells to Prevent GVHD While Conserving Immunity to Viruses and Leukemia.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- Novel treatment of severe combined immunodeficiency utilizing ex-vivo T-cell depleted haploidentical hematopoietic stem cell transplantation and CD45RA+ depleted donor lymphocyte infusions.Orphanet journal of rare diseases · 2016Article
- Allo-reactive T cells for the treatment of hematological malignancies.Molecular oncology · 2015Review
- Graft versus leukemia response without graft-versus-host disease elicited by adoptively transferred multivirus-specific T-cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2015Article
- Engineering human peripheral blood stem cell grafts that are depleted of naïve T cells and retain functional pathogen-specific memory T cells.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2014Article
- Alloreactivity of virus-specific T cells: possible implication of graft-versus-host disease and graft-versus-leukemia effects.Frontiers in immunology · 2013Review
- Activation-induced CD137 is a fast assay for identification and multi-parameter flow cytometric analysis of alloreactive T cells.Clinical and experimental immunology · 2013Article
- Dual receptor T cells mediate pathologic alloreactivity in patients with acute graft-versus-host disease.Science translational medicine · 2013Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
T cell responses to allogeneic targets arise predominantly from the naïve pool. However, in humans, the risk of graft-versus-host disease is increased if the donor has circulating T cells recognizing multiple persistent DNA viruses, suggesting that memory T cells also contribute to the alloresponse. To examine HLA alloreactivity, we used flow cytometry-based proliferation and cytokine production assays. We identified the clonal identity of virus-specific T cells cross-reacting with HLA-disparate targets by sequencing the T cell receptor β chains in virus-specific T cell lines restimulated with cognate and HLA-disparate targets and sorting these chains according to cytokine response. We confirmed that naïve T cells from cord blood and adult individuals responded to HLA-mismatched target cells. In addition, in adults, we identified memory T cells responding by cytokine release to HLA-mismatched targets both in direct assays and after 8 days of culture with allogeneic stimulator cells. Epstein-Barr virus-specific and cytomegalovirus-specific T cells, tested against a panel of 30 T cell antigen-presenting cells with a broad coverage of the most prominent HLA types, displayed specificity for certain mismatched HLA alleles. Sequencing of the T cell receptor β chain demonstrated a clonotypic identity of cells that responded to both viral and allogeneic stimulation. These findings show conclusively that alloresponses in humans are not confined to the naïve T cell subset, and that memory viral antigen-specific T cells can cross-react with specific mismatched HLA-peptide complexes not presenting with cytomegalovirus or Epstein-Barr virus peptides.
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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.