Allograft Rejection by Primed/Memory CD8+ T Cells Is CD154 Blockade Resistant: Therapeutic Implications for Sensitized Transplant Recipients

• DOI: 10.4049/jimmunol.169.8.4667
• Publication Date: 2014-04-21T00:03:53Z
• Authors: Yuan Zhai; Lingzhong Meng; Feng Gao; Ronald W. Busuttil; Jerzy W. Kupiec-W...
• Keywords: CD154; Memory T cell

We have shown that CD8(+) CTLs are the key mediators of accelerated rejection, and T cells represent prime targets CD154 blockade in sensitized mouse recipients cardiac allografts. However, current protocols require at time sensitization, whereas delayed treatment fails to affect graft rejection recipients. To elucidate mechanisms costimulation blockade-resistant improve efficacy CD154-targeted therapy, we found alloreactive were activated despite hosts. Comparative CD8 cell activation study naive vs primed hosts has although both primed/memory relied on CD28 for their activation, only naive, not primed/memory, depend signaling differentiate into CTL effector cells. Adjunctive therapy was designed accordingly deplete before blockade. Indeed, unlike anti-CD154 monotherapy, transient depletion around engraftment significantly improved Hence, this report provides evidence 1) differential requirement signals cells, 2) successful clinically relevant achieve stable long term acceptance.