Analysis of the circulating Th1/Th17 lymphocyte repertoire after hematopoietic stem cell transplant may reveal opportunistic fungal infections rather than GvHD reaction

Human Th17 lymphocytes have been suggested to play a role in the pathogenesis of Graft versus Host Disease (GvHD). However, their actual involvement has not been clarified so far. We analysed the T cell recovery in the peripheral blood of 30 paediatric patients at different time intervals after allogeneic hematopoietic stem cell transplantation (HSCT). We investigated the Th1 (CD4+CD161-CXCR3+CCR6-), Th1/Th17 (CD4+CD161+CXCR3+CCR6+) and Th17 (CD4+CD161+CXCR3-CCR6+) cell subsets repertoire in relation with the GVHD onset, the occurrence of opportunistic infections and/or viral reactivation. In the first 90 days after HSCT, we found no significant difference between patients developing or not acute GVHD. On the other hand, patients affected by chronic GVHD display a sharp reduction of circulating CD4+ lymphocytes. In addition, they were significantly enriched in CD4+CD161+. Analysis of cytokine production revealed that chronic GVHD patients display an increased production of IFN-gamma and IL-17. In patients with acute GVHD, increases of IFN-gamma and IL-17 production were statistically significant, however, no correlation could be found between surface phenotype and cytokine production. On the other hand, in four patients a clear correlation could be observed between the onset of Candida infection and increases of circulating IL-17-producing Th17 cells. Th17 increases were transient and paralleled the course of infection. Our data suggest that chronic GvHD might involve Th1/Th17 cells. More importantly, they show that monitoring Th17 cell populations may provide an useful information on the onset and the severity of opportunistic fungal infections.