The Induction and Maintenance of Transplant Tolerance Engages Both Regulatory and Anergic CD4⁺ T cells.

ABSTRACT: Therapeutic tolerance to self-antigens or foreign antigens is thought to depend on constant vigilance by Foxp3⁺ regulatory T cells (Tregs). Previous work using a pancreatic islet allograft model and a short pulse of CD3 antibody therapy has shown that CD8⁺ T cells become anergic and use TGFβ and coinhibitory signaling as their contribution to the tolerance process. Here, we examine the role of CD4⁺ T cells in tolerization by CD3 antibodies. We show that both Foxp3⁺ Tregs and CD4⁺ T cell anergy play a role in the induction of tolerance and its maintenance. Foxp3⁺ Tregs resisted CD3 antibody-mediated depletion, unlike intragraft Th1 CD4⁺ lymphocytes coexpressing granzyme B and Tbx21, which were selecti

SUBMITTER: Besancon A 

PROVIDER: S-EPMC5337867 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature