Fig. 1. The role of Tregs in direct and indirect allorecognition pathways in graft rejection. This figure illustrates the role of Tregs in suppressing immune responses and preventing graft damage through direct and indirect allorecognition pathways. In the direct pathway, donor graft cells present alloantigens to recipient CD4+ T cells, while in the indirect pathway, recipient APCs present processed donor peptides. Both pathways activate CD8+ T cells and B cells, potentially leading to graft damage. Tregs inhibit T cell activation by depriving effector T cells of IL-2 (via CD25), suppressing dendritic cells through the CTLA-4/CD80 axis, and producing inhibitory cytokines (IL-10, IL-35, and TGF-β). They also modulate B cells via the PD-1/PD-L1 axis and generate adenosine (through CD39/CD73) to protect the graft. MHCII, major histocompatibility complex class II; TCR, T cell receptor; Treg, regulatory T cell; PD-1, programmed cell death protein 1; IL, interleukin; IFN-γ, interferon gamma; ADCC, antibody-dependent cell-mediated cytotoxicity; APC, antigen-presenting cell; TGF, transforming growth factor; DC, dendritic cell; CTLA-4, cytotoxic T-lymphocyte-associated protein 4.