Operational tolerance following intestinal transplantation: A case report with comprehensive immune follow-up from...

Operational tolerance after intestinal transplantation is exceptionally rare, with few reported cases and limited mechanistic understanding. We describe a 12-year-old girl who underwent multivisceral transplantation and subsequently developed graft-versus-host disease (GvHD) followed by Epstein-Barr virus-associated posttransplant lymphoproliferative disease. Due to severe posttransplant lymphoproliferative disease complications, immunosuppression was withdrawn 8 months posttransplant. The patient achieved viral remission and has remained free of rejection for more than 3 years without immunosuppressive therapy. Comprehensive immunological analyses demonstrated stable graft function, absence of donor-specific antibodies, preserved antiviral immunity, and donor-recipient immune coexistence within the graft. Graft-resident regulatory T cells displayed enhanced proliferative and inhibitory features despite stable frequencies. Longitudinal TCR-β repertoire analysis revealed a profound immune "reset" and reprogramming following GvHD. This case provides new evidence that GvHD-associated immune remodeling, together with functional specialization of local regulatory T cells, may constitute the underlying mechanism of long-term graft acceptance.