Decreased levels of circulating IL17-producing CD161+CCR6+ T cells are associated with graft-versus-host disease after allogeneic stem cell transplantation

• Published in: PloS one 2012-12, Vol.7 (12), p.e50896-e50896
• Main Authors: van der Waart, Anniek B, van der Velden, Walter J F M, van Halteren, Astrid G S, Leenders, Marij J L G, Feuth, Ton, Blijlevens, Nicole M A, van der Voort, Robbert, Dolstra, Harry
• Format: Article
• Language: English
• Subjects: Adult; Biology; Bone marrow; Case-Control Studies; CCL20 protein; CCR6 protein; CD4 antigen; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; Cell Movement - drug effects; Chemokine CCL20 - metabolism; Chemokines; Cyclosporine - pharmacology; Cyclosporins; Cytokines; Cytotoxicity; Efflux; Female; Graft versus host disease; Graft vs Host Disease - blood; Graft vs Host Disease - immunology; Graft vs Host Disease - therapy; Graft-versus-host reaction; Growth factors; Hematology; Histocompatibility Testing; Humans; Immunologic Memory - drug effects; Interferon-gamma - biosynthesis; Interleukin 1; Interleukin 17; Interleukin-17 - biosynthesis; Interleukin-17 - blood; Laboratories; Leukemia; Lymphocytes; Lymphocytes T; Male; Medicine; Middle Aged; Multivariate Analysis; NK Cell Lectin-Like Receptor Subfamily B - metabolism; Permeability; Phenotype; Receptors, CCR6 - metabolism; Recovery of function; Stem Cell Transplantation; Stem cells; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Tapering; Tissues; Transplantation; Transplantation, Homologous; Transplants & implants; Young Adult; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0050896

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.