title: Regulatory T cell expression of CLA or α(4)β(7) and skin or gut acute GVHD outcomes.
abstract: Regulatory T cells (Tregs) are a suppressive subset of CD4(+) T lymphocytes implicated in the prevention of acute GVHD (aGVHD) after allo-SCT (ASCT). To determine whether increased frequency of Tregs with a skin-homing (cutaneous lymphocyte Ag, CLA(+)) or a gut-homing (α(4)β(7)(+)) phenotype is associated with reduced risk of skin or gut aGVHD, respectively, we quantified circulating CLA(+) or α(4)β(7)(+) on Tregs at the time of neutrophil engraftment in 43 patients undergoing ASCT. Increased CLA(+) Tregs at engraftment was associated with the prevention of skin aGVHD (2.6 vs 1.7%; P=0.038 (no skin aGVHD vs skin aGVHD)), and increased frequencies of CLA(+) and α(4)β(7)(+) Tregs were negatively correlated with severity of skin aGVHD (odds ratio (OR), 0.67; 95% confidence interval (CI), 0.46-0.98; P=0.041) or gut aGVHD (OR, 0.93; 95% CI, 0.88-0.99; P=0.031), respectively. This initial report suggests that Treg tissue-homing subsets help to regulate organ-specific risk and severity of aGVHD after human ASCT. These results need to be validated in a larger, multicenter cohort.
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232-2905, USA.
authors.forename: B G
authors.initials: BG
authors.lastname: Engelhardt
authors.forename: M
authors.initials: M
authors.lastname: Jagasia
authors.forename: B N
authors.initials: BN
authors.lastname: Savani
authors.forename: N L
authors.initials: NL
authors.lastname: Bratcher
authors.forename: J P
authors.initials: JP
authors.lastname: Greer
authors.forename: A
authors.initials: A
authors.lastname: Jiang
authors.forename: A A
authors.initials: AA
authors.lastname: Kassim
authors.forename: P
authors.initials: P
authors.lastname: Lu
authors.forename: F
authors.initials: F
authors.lastname: Schuening
authors.forename: S M
authors.initials: SM
authors.lastname: Yoder
authors.forename: M T
authors.initials: MT
authors.lastname: Rock
authors.forename: J E
authors.initials: JE
authors.lastname: Crowe
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis* / Q000276:immunology; D015331:Cohort Studies; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D016023:Integrins / Q000096:biosynthesis* / Q000276:immunology; D007410:Intestinal Diseases / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000276:immunology; D008875:Middle Aged; D012871:Skin Diseases / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; C063419:CTAGE1 protein, human; D016207:Cytokines; D016023:Integrins; D008562:Membrane Glycoproteins; C071777:integrin alpha4beta7