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

• Published in: Frontiers in immunology Vol. 15; p. 1411392
• Main Authors: Shaikh, Ahmad, Gangaplara, Arunakumar, Kone, Abdoul, Almengo, Katherine, Kabore, Mariama D., Ali, Mohamed A.E., Xu, Xin, Saxena, Ankit, Lopez-Ocasio, Maria, McCoy, J. Philip, Fitzhugh, Courtney D.
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 16.09.2024
• Subjects: Animals; chimerism; Galectin 1 - immunology; Galectin 1 - metabolism; galectin-1; Graft Rejection - immunology; Graft Survival - immunology; haplo-HCT; Hematopoietic Stem Cell Transplantation; Immune Tolerance; Immunology; Major Histocompatibility Complex - immunology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; T-Lymphocytes, Regulatory - immunology; tolerance; Transplantation, Homologous; Tregs; haplo-HCT; chimerism; Tregs; tolerance; galectin-1
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2024.1411392

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.