Decreased Levels of Circulating IL17-Producing CD161(+)CCR6(+) T Cells Are Associated with Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation
SourcePLoS One, 7, 12, (2012), article e50896
Article / Letter to editor
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Laboratory of Hematology
Epidemiology, Biostatistics & HTA
SubjectN4i 2: Invasive mycoses and compromised host ONCOL 3: Translational research; NCEBP 2: Evaluation of complex medical interventions; NCMLS 2: Immune Regulation ONCOL 3: Translational research
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 IFNgamma 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.
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