Low percentages of circulating CD8+/CD45RA+ human T lymphocytes expressing β7 integrin correlate with the occurrence of intestinal acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

M. Antonietta Avanzini, Rita Maccario, Franco Locatelli, Sebastian Giebel, Conceiçao Dos Santos, Maria Ester Bernardo, Daria Pagliara, Daniela Montagna, Stefania Longo, Giovanni Amendola, Massimo Marconi

Research output: Contribution to journalArticle

Abstract

Objective: Effector phase of acute graft-versus-host disease (a-GVHD) is mainly mediated by donor-derived, anti-host cytotoxic T cells. T-cell homing into gut-associated lymphoid tissues is ascribed to the α4β7 integrin. We reasoned that development of intestinal a-GVHD might be triggered by recruitment in the intestinal mucosa of circulating, alloreactive, α4β7+ donor T cells. Therefore, we evaluated the correlation existing between circulating β7+ T-lymphocyte subsets early after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and occurrence of a-GVHD. Patients and Methods: Surface expression of β7 integrin on T cells was evaluated by means of direct immunofluorescence, in three-color analysis. Sixty-five patients given allo-HSCT were evaluated: 13 of them experienced intestinal a-GVHD, 14 developed a-GVHD without intestinal involvement, and 38 did not develop a-GVHD. Patients were studied early after initial signs of hematologic reconstitution and before occurrence of a-GVHD. Results: We found a significantly higher absolute number of CD8+ and a significantly lower percentage of CD8+CD45RA+β7+ T cells in patients with intestinal a-GVHD than in patients with a-GVHD without intestinal involvement (p = 0.003 and p = 0.003, respectively) or not experiencing a-GVHD (p = 0.02 and p = 0.002, respectively). In particular, we found that intestinal a-GVHD occurred in over 70% of patients showing an absolute number of CD8+ T cells ≥ 60 × 106/L and a percentage of circulating CD8+CD45RA+β7+ T cells <35%. Conclusion: Measuring the absolute number of CD8+ T cells and percentage of CD8+CD45RA+β7+ T cells at time of hematologic reconstitution may help identify patients at risk of developing intestinal a-GVHD who could benefit from strategies aimed at hampering alloreactive T-cell homing to intestinal mucosa.

Original languageEnglish
Pages (from-to)1429-1434
Number of pages6
JournalExperimental Hematology
Volume34
Issue number10
DOIs
Publication statusPublished - Oct 2006

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Hematopoietic Stem Cell Transplantation
Graft vs Host Disease
Integrins
T-Lymphocytes
Intestinal Mucosa
Tissue Donors
Direct Fluorescent Antibody Technique
T-Lymphocyte Subsets
Lymphoid Tissue
Color

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

Cite this

@article{2cf556a623934f228ddf1dc2f0ef4f3c,
title = "Low percentages of circulating CD8+/CD45RA+ human T lymphocytes expressing β7 integrin correlate with the occurrence of intestinal acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation",
abstract = "Objective: Effector phase of acute graft-versus-host disease (a-GVHD) is mainly mediated by donor-derived, anti-host cytotoxic T cells. T-cell homing into gut-associated lymphoid tissues is ascribed to the α4β7 integrin. We reasoned that development of intestinal a-GVHD might be triggered by recruitment in the intestinal mucosa of circulating, alloreactive, α4β7+ donor T cells. Therefore, we evaluated the correlation existing between circulating β7+ T-lymphocyte subsets early after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and occurrence of a-GVHD. Patients and Methods: Surface expression of β7 integrin on T cells was evaluated by means of direct immunofluorescence, in three-color analysis. Sixty-five patients given allo-HSCT were evaluated: 13 of them experienced intestinal a-GVHD, 14 developed a-GVHD without intestinal involvement, and 38 did not develop a-GVHD. Patients were studied early after initial signs of hematologic reconstitution and before occurrence of a-GVHD. Results: We found a significantly higher absolute number of CD8+ and a significantly lower percentage of CD8+CD45RA+β7+ T cells in patients with intestinal a-GVHD than in patients with a-GVHD without intestinal involvement (p = 0.003 and p = 0.003, respectively) or not experiencing a-GVHD (p = 0.02 and p = 0.002, respectively). In particular, we found that intestinal a-GVHD occurred in over 70{\%} of patients showing an absolute number of CD8+ T cells ≥ 60 × 106/L and a percentage of circulating CD8+CD45RA+β7+ T cells <35{\%}. Conclusion: Measuring the absolute number of CD8+ T cells and percentage of CD8+CD45RA+β7+ T cells at time of hematologic reconstitution may help identify patients at risk of developing intestinal a-GVHD who could benefit from strategies aimed at hampering alloreactive T-cell homing to intestinal mucosa.",
author = "Avanzini, {M. Antonietta} and Rita Maccario and Franco Locatelli and Sebastian Giebel and Santos, {Concei{\cc}ao Dos} and Bernardo, {Maria Ester} and Daria Pagliara and Daniela Montagna and Stefania Longo and Giovanni Amendola and Massimo Marconi",
year = "2006",
month = "10",
doi = "10.1016/j.exphem.2006.06.006",
language = "English",
volume = "34",
pages = "1429--1434",
journal = "Experimental Hematology",
issn = "0301-472X",
publisher = "Elsevier Inc.",
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TY - JOUR

T1 - Low percentages of circulating CD8+/CD45RA+ human T lymphocytes expressing β7 integrin correlate with the occurrence of intestinal acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

AU - Avanzini, M. Antonietta

AU - Maccario, Rita

AU - Locatelli, Franco

AU - Giebel, Sebastian

AU - Santos, Conceiçao Dos

AU - Bernardo, Maria Ester

AU - Pagliara, Daria

AU - Montagna, Daniela

AU - Longo, Stefania

AU - Amendola, Giovanni

AU - Marconi, Massimo

PY - 2006/10

Y1 - 2006/10

N2 - Objective: Effector phase of acute graft-versus-host disease (a-GVHD) is mainly mediated by donor-derived, anti-host cytotoxic T cells. T-cell homing into gut-associated lymphoid tissues is ascribed to the α4β7 integrin. We reasoned that development of intestinal a-GVHD might be triggered by recruitment in the intestinal mucosa of circulating, alloreactive, α4β7+ donor T cells. Therefore, we evaluated the correlation existing between circulating β7+ T-lymphocyte subsets early after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and occurrence of a-GVHD. Patients and Methods: Surface expression of β7 integrin on T cells was evaluated by means of direct immunofluorescence, in three-color analysis. Sixty-five patients given allo-HSCT were evaluated: 13 of them experienced intestinal a-GVHD, 14 developed a-GVHD without intestinal involvement, and 38 did not develop a-GVHD. Patients were studied early after initial signs of hematologic reconstitution and before occurrence of a-GVHD. Results: We found a significantly higher absolute number of CD8+ and a significantly lower percentage of CD8+CD45RA+β7+ T cells in patients with intestinal a-GVHD than in patients with a-GVHD without intestinal involvement (p = 0.003 and p = 0.003, respectively) or not experiencing a-GVHD (p = 0.02 and p = 0.002, respectively). In particular, we found that intestinal a-GVHD occurred in over 70% of patients showing an absolute number of CD8+ T cells ≥ 60 × 106/L and a percentage of circulating CD8+CD45RA+β7+ T cells <35%. Conclusion: Measuring the absolute number of CD8+ T cells and percentage of CD8+CD45RA+β7+ T cells at time of hematologic reconstitution may help identify patients at risk of developing intestinal a-GVHD who could benefit from strategies aimed at hampering alloreactive T-cell homing to intestinal mucosa.

AB - Objective: Effector phase of acute graft-versus-host disease (a-GVHD) is mainly mediated by donor-derived, anti-host cytotoxic T cells. T-cell homing into gut-associated lymphoid tissues is ascribed to the α4β7 integrin. We reasoned that development of intestinal a-GVHD might be triggered by recruitment in the intestinal mucosa of circulating, alloreactive, α4β7+ donor T cells. Therefore, we evaluated the correlation existing between circulating β7+ T-lymphocyte subsets early after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and occurrence of a-GVHD. Patients and Methods: Surface expression of β7 integrin on T cells was evaluated by means of direct immunofluorescence, in three-color analysis. Sixty-five patients given allo-HSCT were evaluated: 13 of them experienced intestinal a-GVHD, 14 developed a-GVHD without intestinal involvement, and 38 did not develop a-GVHD. Patients were studied early after initial signs of hematologic reconstitution and before occurrence of a-GVHD. Results: We found a significantly higher absolute number of CD8+ and a significantly lower percentage of CD8+CD45RA+β7+ T cells in patients with intestinal a-GVHD than in patients with a-GVHD without intestinal involvement (p = 0.003 and p = 0.003, respectively) or not experiencing a-GVHD (p = 0.02 and p = 0.002, respectively). In particular, we found that intestinal a-GVHD occurred in over 70% of patients showing an absolute number of CD8+ T cells ≥ 60 × 106/L and a percentage of circulating CD8+CD45RA+β7+ T cells <35%. Conclusion: Measuring the absolute number of CD8+ T cells and percentage of CD8+CD45RA+β7+ T cells at time of hematologic reconstitution may help identify patients at risk of developing intestinal a-GVHD who could benefit from strategies aimed at hampering alloreactive T-cell homing to intestinal mucosa.

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