TY - JOUR
T1 - Tissue-specific regulatory T cells
T2 - Biomarker for acute graft-vs-host disease and survival
AU - Engelhardt, Brian G.
AU - Sengsayadeth, Salyka M.
AU - Jagasia, Madan
AU - Savani, Bipin N.
AU - Kassim, Adetola A.
AU - Lu, Pengcheng
AU - Shyr, Yu
AU - Yoder, Sandra M.
AU - Rock, Michael T.
AU - Crowe, James E.
N1 - Funding Information:
This work was supported by the National Institutes of Health/National Cancer Institute Grant K12 CA090625 , the American Cancer Society–Institutional Research Grant ( #IRG-58-009-48 ) and the Sartain-Lanier Family Foundation .
PY - 2012/12
Y1 - 2012/12
N2 - 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.
AB - 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.
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U2 - 10.1016/j.exphem.2012.08.002
DO - 10.1016/j.exphem.2012.08.002
M3 - Article
C2 - 22885125
AN - SCOPUS:84868707576
VL - 40
SP - 974-982.e1
JO - Experimental Hematology
JF - Experimental Hematology
SN - 0301-472X
IS - 12
ER -