James Crowe
Faculty Member
Last active: 3/31/2019

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

Engelhardt BG, Sengsayadeth SM, Jagasia M, Savani BN, Kassim AA, Lu P, Shyr Y, Yoder SM, Rock MT, Crowe JE
Exp Hematol. 2012 40 (12): 974-982.e1

PMID: 22885125 · PMCID: PMC3611587 · DOI:10.1016/j.exphem.2012.08.002

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 (α(4)β(7)(+)) subsets were identified by flow cytometry, and patients were divided into high CLA(+) Tregs or high α(4)β(7)(+) Tregs groups, using the 75(th) 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 α(4)β(7)(+) Tregs at engraftment, respectively (high CLA(+) Tregs, 24.0% vs low CLA(+) Tregs, 55.1%; p = 0.011 for skin aGVHD or high α(4)β(7)(+) Tregs, 47.3% vs low α(4)β(7)(+) 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 α(4)β(7)(+) Tregs (p = 0.039, p = 0.010). These results suggest that a threshold value for CLA(+) or α(4)β(7)(+) 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.

Copyright © 2012 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

MeSH Terms (15)

Adult Aged Biomarkers Female Graft vs Host Disease Hematopoietic Stem Cell Transplantation Humans Intestines Male Middle Aged Organ Specificity Skin T-Lymphocytes, Regulatory Transplantation, Homologous Young Adult

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