Linked sensitization by memory CD4+ T cells prevents costimulation blockade-induced transplantation tolerance.

ABSTRACT: Dominant infectious tolerance explains how brief tolerance-inducing therapies result in lifelong tolerance to donor antigens and "linked" third-party antigens, while recipient sensitization and ensuing immunological memory prevent the successful induction of transplant tolerance. In this study, we juxtapose these 2 concepts to test whether mechanisms of dominant infectious tolerance can control a limited repertoire of memory T and B cells. We show that sensitization to a single donor antigen is sufficient to prevent stable transplant tolerance, rendering it unstable. Mechanistic studies revealed that recall antibody responses and memory CD8+ T cell expansion were initially controlled, but memory CD4+Foxp3- T cell (Tconv) responses were not. Remarkably, naive donor-specific Tconvs at tolera

SUBMITTER: Andrade MS 

PROVIDER: S-EPMC9220839 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature