title: Protection against bronchiolitis obliterans syndrome is associated with allograft CCR7+ CD45RA- T regulatory cells.
abstract: Bronchiolitis obliterans syndrome (BOS) is the major obstacle to long-term survival after lung transplantation, yet markers for early detection and intervention are currently lacking. Given the role of regulatory T cells (Treg) in modulation of immunity, we hypothesized that frequencies of Treg in bronchoalveolar lavage fluid (BALF) after lung transplantation would predict subsequent development of BOS. Seventy BALF specimens obtained from 47 lung transplant recipients were analyzed for Treg lymphocyte subsets by flow cytometry, in parallel with ELISA measurements of chemokines. Allograft biopsy tissue was stained for chemokines of interest. Treg were essentially all CD45RA(-), and total Treg frequency did not correlate to BOS outcome. The majority of Treg were CCR4(+) and CD103(-) and neither of these subsets correlated to risk for BOS. In contrast, higher percentages of CCR7(+) Treg correlated to reduced risk of BOS. Additionally, the CCR7 ligand CCL21 correlated with CCR7(+) Treg frequency and inversely with BOS. Higher frequencies of CCR7(+) CD3(+)CD4(+)CD25(hi)Foxp3(+)CD45RA(-) lymphocytes in lung allografts is associated with protection against subsequent development of BOS, suggesting that this subset of putative Treg may down-modulate alloimmunity. CCL21 may be pivotal for the recruitment of this distinct subset to the lung allograft and thereby decrease the risk for chronic rejection.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of California Los Angeles, Los Angeles, California, United States of America. a.gregson@ucla.edu
authors.forename: Aric L
authors.initials: AL
authors.lastname: Gregson
authors.forename: Aki
authors.initials: A
authors.lastname: Hoji
authors.forename: Vyacheslav
authors.initials: V
authors.lastname: Palchevskiy
authors.forename: Scott
authors.initials: S
authors.lastname: Hu
authors.forename: S Samuel
authors.initials: SS
authors.lastname: Weigt
authors.forename: Eileen
authors.initials: E
authors.lastname: Liao
authors.forename: Ariss
authors.initials: A
authors.lastname: Derhovanessian
authors.forename: Rajeev
authors.initials: R
authors.lastname: Saggar
authors.forename: Sophie
authors.initials: S
authors.lastname: Song
authors.forename: Robert
authors.initials: R
authors.lastname: Elashoff
authors.forename: Otto O
authors.initials: OO
authors.lastname: Yang
authors.forename: John A
authors.initials: JA
authors.lastname: Belperio
mesh_terms: D001989:Bronchiolitis Obliterans / Q000276:immunology / Q000517:prevention & control*; D001992:Bronchoalveolar Lavage Fluid; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006084:Graft Rejection; D006801:Humans; D007150:Immunohistochemistry; D017493:Leukocyte Common Antigens / Q000276:immunology*; D016040:Lung Transplantation; D054400:Receptors, CCR7 / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: C515370:CCR7 protein, human; D054400:Receptors, CCR7; D017493:Leukocyte Common Antigens