title: Comparative analysis of FoxP3(+) regulatory T cells in the target tissues and blood in chronic graft versus host disease.
abstract: Activation and migration of regulatory T cells (Treg) into tissue is critical in control of inflammation, but has not been examined extensively in chronic graft versus host disease (cGVHD). In parallel studies of tissues and blood, we determined that FoxP3(+) T cells increased in proportion to T effectors (Teff) in tissue infiltrates in oral and cutaneous lichenoid cGVHD. These FoxP3(+) cells expressed distinguishing phenotypic and functional markers of Treg (CD3(+), CD4(+), CD27(+), ICOS(+) and CD39(+)), not found on FoxP3(-) Teff. Both Teff and FoxP3(+) Treg expressed T-bet and the chemokine receptor CXCR3, however, consistent with a common mechanism of chemokine-mediated migration into tissue. Furthermore, functional markers (ICOS and CD39) and chemokine receptors (CXCR3) were both present in a higher proportion of FoxP3(+) cells in tissues than in peripheral blood, consistent with recruitment and activation of Treg in cGVHD target tissues. Finally, the 'activated' CD45RA(-)FoxP3(hi) subset of Treg cells, which highly express functional markers, were found in comparable frequencies in cGVHD patients and normal controls, despite a significant deficit in naive 'resting' Treg. These findings are consistent with Treg capacity to upregulate functional markers and traffick into tissue in cGVHD.
authors.affiliation: 1] Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA [2] Department of Otolaryngology Head and Neck Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Imanguli
authors.affiliation: Dermatology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: E W
authors.initials: EW
authors.lastname: Cowen
authors.affiliation: Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: J
authors.initials: J
authors.lastname: Rose
authors.affiliation: Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: S
authors.initials: S
authors.lastname: Dhamala
authors.affiliation: Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, Bethesda, MD, USA.
authors.forename: W
authors.initials: W
authors.lastname: Swaim
authors.affiliation: Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: S
authors.initials: S
authors.lastname: Lafond
authors.affiliation: Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: B
authors.initials: B
authors.lastname: Yagi
authors.affiliation: Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Gress
authors.affiliation: Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: S Z
authors.initials: SZ
authors.lastname: Pavletic
authors.affiliation: Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: F T
authors.initials: FT
authors.lastname: Hakim
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D001081:Apyrase / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006086:Graft vs Host Disease / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D054367:Receptors, CXCR3 / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D017252:CD3 Complex; D015704:CD4 Antigens; C515187:CXCR3 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; D054367:Receptors, CXCR3; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D001081:Apyrase; C067869:CD39 antigen