Galactin-1 favors engraftment in sickle cell disease patients after haploidentical hematopoietic stem cell transplantation and in murine MHC-mismatched allotransplantation

Abstract

Abstract Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is associated with increased risk of allograft rejection. Understanding the mechanisms of graft rejection and tolerance induction are critical for improving HSCT outcome. Recently, we performed a proteomic analysis using plasma samples from sickle cell disease (SCD) patients who underwent haplo-HSCT and found that galectin-1 (Gal-1) levels were significantly higher in engrafted patients. Here, we studied major histocompatibility complex (MHC)-mismatched allo-HSCT murine model to better understand the role of Gal-1 in immune tolerance. Transplanted mice were classified into either rejected (cyclophosphamide/sirolimus alone) or engrafted (cyclophosphamide and sirolimus) based on our previous findings. In rejected mice we noted significantly higher frequencies of CD4+T, CD8+T, NK cells, IFN-γ TNF-α producing CD4+T cells, and also IFN-γ producing DCs and macrophages. Importantly, in engrafted mice we found significantly increased frequencies of Tregs and IL-10 producing CD4+T and Tr1 cells, and the proportion of these cells expressing Gal-1 was significantly higher. Further, we detected a significant increase in Gal-1 levels in plasma of engrafted mice, and this corroborated with our data from engrafted patients. Here, we have shown for the first time that not only Gal-1 favors engraftment in SCD patients who underwent haplo-HSCT, but Gal-1 also contributes to HSC engraftment in our MHC-mismatched murine model. Taken together, our results demonstrate that Gal-1 expressing Tregs and Tr1 cells may play an essential role in inducing immune tolerance and stable mixed chimerism after HSCT.