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Graft-Versus-Host Disease

Expression of α4β7 integrin on memory CD8+ T cells at the presentation of acute intestinal GVHD

Abstract

Acute intestinal GVHD remains a major source of morbidity after allogeneic hematopoietic cell transplantation (HCT). α4β7 integrin is a cell surface molecule that mediates lymphocyte trafficking to intestinal tissue. In this analysis, peripheral blood was collected at the time of presentation of symptoms of acute GVHD and before any treatment. In all, 45 samples were collected and divided into three groups on the basis of subsequent evaluation: intestinal GVHD (n=15), skin GVHD (n=20) and no GVHD (n=10). Two patients developed intestinal GVHD after DLI. The no-GVHD group comprised 10 patients who presented with suspicious symptoms, but evaluation yielded other etiologies. Analysis by flow cytometry showed that intestinal GVHD patients had a significantly higher percentage of α4β7 integrin-expressing memory CD8+ T cells (median 7.69%; lower and upper quartiles, 1.06% and 11.64%, respectively) compared with patients with skin GVHD (1.26%; 0.57% and 2.49%) and no GVHD (0.96%; 0.44% and 1.85%), P=0.03. No differences were found in α4β7 expression in any CD4+ T-cell subsets or naive CD8+ T cells. This study adds to the evidence that α4β7 integrin is involved in lymphocyte trafficking in acute intestinal GVHD.

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Acknowledgements

This research was supported in part by NIH grants AI29530 and HL070149, the Ted and Ellen Pasquarello Research Fund, the Wernick Family Fund for Cancer Care, the Rogers Family Foundation and the Leukemia & Lymphoma Society. This research was presented in abstract form at the American Society for Bone Marrow Transplantation (ASBMT) Tandem Meetings in San Diego, CA from 1 to 5 February 2012.

Author contributions: Y Chen designed the research, enrolled patients, performed research, collected data, analyzed data and wrote the manuscript. S McDonough processed specimens, performed research, collected data and reviewed the manuscript. H Chen analyzed the data, wrote part of the manuscript and reviewed the manuscript. J Kennedy managed the data and reviewed the manuscript. C Illiano collected specimens, managed the data and reviewed the manuscript. E Attar, K Ballen, B Dey and S McAfee enrolled patients and reviewed the manuscript. M Jagasia, J Ritz and R Soiffer designed the research and reviewed the manuscript. T Spitzer designed the research, enrolled patients and reviewed the manuscript.

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Correspondence to Y-B Chen.

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Dr Chen receives funding to conduct clinical research from Millennium Pharmaceuticals, Inc. The other authors declare no conflict of interest.

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Chen, YB., McDonough, S., Chen, H. et al. Expression of α4β7 integrin on memory CD8+ T cells at the presentation of acute intestinal GVHD. Bone Marrow Transplant 48, 598–603 (2013). https://doi.org/10.1038/bmt.2012.191

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