Interleukin-17-producing cells increase among CD4+ lymphocytes before overt manifestation of acute graft-versus-host disease.

Interleukin-17A is a hallmark of a subset of CD4+ lymphocytes called T(H)17. Allogeneic hematopoietic stem cell transplantation (HSCT) induces an immune response that facilitates graft acceptance, but if clinically apparent as acute graft-versus-host disease (aGvHD), it may adversely affect transplantation outcomes. TH17 cells are involved in the inflammatory processes associated with several diseases, including inflammatory bowel disease (IBD) as a prototype. In this study we investigated the presence of IL-17-producing cells among peripheral blood mononuclear cells (PBMC) of patients after HSCT. The 48 patients of median age 45 years (range, 1.0-64 years), experienced hematologic malignancies (n=45) or nonmalignant disorders (n=3), treated with matched unrelated (n=24) or sibling (n=24) transplants. We examined IL-17-producing cells in alloreactive reactions after HSCT. PBMC were stimulated with BD Leukocyte Activation Cocktail (Ionomycin, Brefeldin A, and phorbol myristic acetate (PMA)) in the presence of BD GolgiStop. After stimulation the cells were labeled with anti-CD4 and intracellular anti-IL-17A monoclonal antibodies. IL-17+ cell proportions were analyzed in the CD4+ lymphocyte gate. We observed that patients at the time of hematologic reconstitution had higher proportions of IL-17-producing cells than healthy control subjects (0.73±0.13 vs 0.19±0.06%; P=.019). Fourteen patients displayed the first symptoms of aGvHD at the time of hematologic reconstitution, when they showed lower proportions of IL-17+ cells among CD4+ lymphocytes than their counterparts lacking aGvHD at a similar time after transplantation (0.29±0.09 vs 0.73±0.13%; P=.024). Eight patients developed aGvHD after hematologic reconstitution (median, 34 days). All of these patients displayed lower proportions of IL-17-producing CD4+ cells on the day of aGvHD compared with their initial measurements preceding this complication (0.34±0.14 vs 1.07±0.37%; P=.01).