title: Decreased levels of circulating IL17-producing CD161+CCR6+ T cells are associated with graft-versus-host disease after allogeneic stem cell transplantation.
abstract: The C-type lectin-like receptor CD161 is a well-established marker for human IL17-producing T cells, which have been implicated to contribute to the development of graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (allo-SCT). In this study, we analyzed CD161(+) T cell recovery, their functional properties and association with GVHD occurrence in allo-SCT recipients. While CD161(+)CD4(+) T cells steadily recovered, CD161(hi)CD8(+) T cell numbers declined during tapering of Cyclosporine A (CsA), which can be explained by their initial growth advantage over CD161(neg/low)CD8(+) T cells due to ABCB1-mediated CsA efflux. Interestingly, occurrence of acute and chronic GVHD was significantly correlated with decreased levels of circulating CD161(+)CD4(+) as well as CD161(hi)CD8(+) T cells. In addition, these subsets from transplanted patients secreted high levels of IFNγ and IL17. Moreover, we found that CCR6 co-expression by CD161(+) T cells mediated specific migration towards CCL20, which was expressed in GVHD biopsies. Finally, we demonstrated that CCR6(+) T cells indeed were present in these CCL20(+) GVHD-affected tissues. In conclusion, we showed that functional CD161(+)CCR6(+) co-expressing T cells disappear from the circulation and home to GVHD-affected tissue sites. These findings support the hypothesis that CCR6(+)CD161-expressing T cells may be involved in the immune pathology of GVHD following their CCL20-dependent recruitment into affected tissues.
authors.affiliation: Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Anniek B
authors.initials: AB
authors.lastname: van der Waart
authors.forename: Walter J F M
authors.initials: WJ
authors.lastname: van der Velden
authors.forename: Astrid G S
authors.initials: AG
authors.lastname: van Halteren
authors.forename: Marij J L G
authors.initials: MJ
authors.lastname: Leenders
authors.forename: Ton
authors.initials: T
authors.lastname: Feuth
authors.forename: Nicole M A
authors.initials: NM
authors.lastname: Blijlevens
authors.forename: Robbert
authors.initials: R
authors.lastname: van der Voort
authors.forename: Harry
authors.initials: H
authors.lastname: Dolstra
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016022:Case-Control Studies; D002465:Cell Movement / Q000187:drug effects; D054418:Chemokine CCL20 / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood / Q000276:immunology* / Q000628:therapy*; D006650:Histocompatibility Testing; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects; D007371:Interferon-gamma / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000097:blood; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000378:metabolism*; D010641:Phenotype; D054399:Receptors, CCR6 / Q000378:metabolism*; D033581:Stem Cell Transplantation; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: C106311:CCR6 protein, human; D054418:Chemokine CCL20; D020381:Interleukin-17; D055651:NK Cell Lectin-Like Receptor Subfamily B; D054399:Receptors, CCR6; D007371:Interferon-gamma; D016572:Cyclosporine