Absence of recipient C3aR1 signaling limits expansion and differentiation of alloreactive CD8+ T cell immunity and prolongs murine cardiac allograft survival.

ABSTRACT: Activation, differentiation, and expansion of alloreactive CD8+ T cells, the dominant effectors that mediate murine heart allograft rejection, requires allorecognition, costimulation, and cytokine-initiated signals. While previous work showed that alloreactive CD4+ T cell immunity entails immune cell-produced and locally activated complement, whether and how C3a receptor 1 (C3aR1) signaling impacts transplant outcomes and the mechanisms linking C3aR1 to alloreactive CD8+ T cell activation/expansion remain unclear. Herein we show that recipient C3aR1 deficiency or pharmacological C3aR1 blockade synergizes with tacrolimus to significantly prolong allograft survival versus tacrolimus-treated controls (median survival time 21 vs. 14 days, P < .05). Recipient C3aR1-deficiency reduced the freque

SUBMITTER: Mathern DR 

PROVIDER: S-EPMC6538425 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature