Galectin-1 is associated with hematopoietic cell engraftment in murine MHC-mismatched allotransplantation

Haploidentical hematopoietic cell transplantation (haplo-HCT) is associated with an increased risk of allograft rejection. Here, we employed a major histocompatibility complex (MHC)-mismatched allogeneic HCT (allo-HCT) murine model to better understand the role of Gal-1 in immune tolerance. Transplanted mice were classified into either rejected or engrafted based on donor chimerism levels. We noted significantly higher frequencies of CD4⁺ T cells, CD8⁺ T cells, natural killer cells, IFN-γ and TNF-α producing CD4⁺ T cells, and IFN-γ producing dendritic cells and macrophages in rejected mice. Conversely, we found significantly increased frequencies of regulatory T cells (Tregs), predominantly Helios⁺, IL-10-producing CD4⁺ T cells, type 1 regulatory (Tr1) cells, and the proportion of Tr1⁺Gal-1⁺ cells in engrafted mice. Further, Gal-1 specific blockade in Tregs reduced suppression of effector T cells in engrafted mice. Lastly, effector T cells from engrafted mice were more prone to undergo apoptosis. Collectively, we have shown that Gal-1 may favor HSC engraftment in an MHC-mismatched murine model. Our results demonstrate that Gal-1-expressing Tregs, especially at earlier time points post-transplant, are associated with inducing immune tolerance and stable mixed chimerism after HCT.