Interleukin-17-Producing T Cells: A New Potential Player Mediating Graft Versus Host Pathology In Patients Undergoing Allogeneic Stem Cell Transplantion

Graft-vs-host disease (GvHD) is a major obstacle to safe allogeneic haematopoietic stem cell transplantation (HSCT), leading to significant morbidity and mortality. Recently, a subset of interleukin (IL)-17-producing cells, named Th17, have been shown to play a central role in the induction of autoimmune-tissue injuries and inflammation. The aim of our study is to analyze the Th17 population in the peripheral blood of transplanted patients experiencing (6) acute, (7) active chronic and (6) chronic GvHD. Both Elispot assay and intracellular staining showed an augmented population of Th17 (both IL-17+/IFN-g− and IL-17+/IFN-g+ producing cells) in patients with both aGVHD and active cGVHD, that can represent up to 2.4% of CD4+ T lymphocytes. In accordance, an increased IL-17 plasma level was detected both in patients with aGVHD (mean IL17A concentration= 14 pg/ml) and active cGVHD (mean IL17A concentration= 12 pg/ml), compared to healthy donors (mean IL17A concentration < 4 pg/ml). Interestingly, the percentage of TH17 cells drastically decreased in patient with quiescent cGVHD. Th17 cells of patients with aGVHD and active cGVHD, were of donor origin, as demonstrated by genotyping, and, in line with what already described, showed high IL23 receptor expression (mean= 40%, range 30%–52%). Noticeably, in the liver and skin GVHD lesions, the solely CD3 cells spontaneously producing cytokines were double positive for INF-γ and IL-17A. Importantly, we demonstrated a strict correlation between the levels of TH17 cells and the clinical status of patients with GVHD. The better understanding of the role played by TH17 in the GVHD pathogenesis could open the way to new highly targeted strategies for the management of GVHD.