Tissue-specific regulatory T cells: Biomarker for acute graft-vs-host disease and survival

Brian G. Engelhardt, Salyka M. Sengsayadeth, Madan Jagasia, Bipin N. Savani, Adetola A. Kassim, Pengcheng Lu, Yu Shyr, Sandra M. Yoder, Michael T. Rock, James E. Crowe

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Regulatory T cells (Tregs) are a subset of CD4+ T cells that are characterized by the expression of CD25 and Foxp3 and are capable of suppressing alloimmune responses. We assessed whether high frequencies of circulating skin or gut tissue-specific Tregs at engraftment could predict acute graft-vs-host disease (aGVHD) incidence and survival in a cohort of hematopoietic cell transplant (HCT) recipients. Tregs were analyzed at engraftment in 74 patients receiving HCT. Treg skin-homing (CLA+) or gut-homing (α4β7 +) subsets were identified by flow cytometry, and patients were divided into high CLA+ Tregs or high α4β7 + Tregs groups, using the 75th percentile of tissue-specific Treg percentages as a threshold. At day +100 post-HCT, the cumulative incidence of any stage skin or gut aGVHD was significantly lower in those patients with high CLA+ Tregs or high α4β7 + Tregs at engraftment, respectively (high CLA+ Tregs, 24.0% vs low CLA+ Tregs, 55.1%; p = 0.011 for skin aGVHD or high α4β7 + Tregs, 47.3% vs low α4β7 + Tregs, 74.5%; p = 0.029 for gut aGVHD). The 2-year probabilities of overall survival and nonrelapse mortality were 73.4% and 7.5% among patients with high frequencies of tissue-specific Tregs vs 49.4% and 36.1% for those with both low CLA+ Tregs and low α4β7 + Tregs (p = 0.039, p = 0.010). These results suggest that a threshold value for CLA+ or α4β7 + Tregs could be used to predict important HCT outcomes, and to direct the rationale use of tissue-specific pre-emptive therapies to decrease clinical aGVHD and improve HCT survival.

Original languageEnglish
Pages (from-to)974-982.e1
JournalExperimental Hematology
Volume40
Issue number12
DOIs
Publication statusPublished - 2012 Dec

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

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