title: Tissue-specific regulatory T cells: biomarker for acute graft-vs-host disease and survival.
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 (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.
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232-2905, USA.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Engelhardt
authors.forename: Salyka M
authors.initials: SM
authors.lastname: Sengsayadeth
authors.forename: Madan
authors.initials: M
authors.lastname: Jagasia
authors.forename: Bipin N
authors.initials: BN
authors.lastname: Savani
authors.forename: Adetola A
authors.initials: AA
authors.lastname: Kassim
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Lu
authors.forename: Yu
authors.initials: Y
authors.lastname: Shyr
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Yoder
authors.forename: Michael T
authors.initials: MT
authors.lastname: Rock
authors.forename: James E
authors.initials: JE
authors.lastname: Crowe
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology* / Q000401:mortality*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007422:Intestines / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009928:Organ Specificity / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D015415:Biomarkers