Decreased Levels of Circulating IL17-Producing CD161.sup.+CCR6.sup.+ T Cells Are Associated with Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation

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.sup.+ T cell re...

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Bibliographic Details
Published in:PloS one 2012-12, Vol.7 (12), p.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:
Analysis
Lectins
Stem cell transplantation
Stem cells
T cells
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Summary: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.sup.+ T cell recovery, their functional properties and association with GVHD occurrence in allo-SCT recipients. While CD161.sup.+ CD4.sup.+ T cells steadily recovered, CD161.sup.hi CD8.sup.+ T cell numbers declined during tapering of Cyclosporine A (CsA), which can be explained by their initial growth advantage over CD161.sup.neg/low CD8.sup.+ T cells due to ABCB1-mediated CsA efflux. Interestingly, occurrence of acute and chronic GVHD was significantly correlated with decreased levels of circulating CD161.sup.+ CD4.sup.+ as well as CD161.sup.hi CD8.sup.+ T cells. In addition, these subsets from transplanted patients secreted high levels of IFN[gamma] and IL17. Moreover, we found that CCR6 co-expression by CD161.sup.+ T cells mediated specific migration towards CCL20, which was expressed in GVHD biopsies. Finally, we demonstrated that CCR6.sup.+ T cells indeed were present in these CCL20.sup.+ GVHD-affected tissues. In conclusion, we showed that functional CD161.sup.+ CCR6.sup.+ co-expressing T cells disappear from the circulation and home to GVHD-affected tissue sites. These findings support the hypothesis that CCR6.sup.+ CD161-expressing T cells may be involved in the immune pathology of GVHD following their CCL20-dependent recruitment into affected tissues.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0050896