Successful desensitization with proteasome inhibition and costimulation blockade in sensitized nonhuman primates.

ABSTRACT: The detrimental effects of donor-directed antibodies in sensitized transplant patients remain a difficult immunologic barrier to successful organ transplantation. Antibody removal is often followed by rebound. Proteasome inhibitors (PIs) deplete antibody-producing plasma cells (PCs) but have shown marginal benefit for desensitization. In an allosensitized nonhuman primate (NHP) model, we observed increased germinal center (GC) formation after PI monotherapy, suggesting a compensatory PC repopulation mediated via GC activation. Here we show that costimulation blockade (CoB) targets GC follicular helper T (Tfh) cells in allosensitized NHPs. Combined PI and CoB significantly reduces bone marrow PCs (CD19⁺CD20^-CD38⁺), Tfh cells (CD4⁺ICOS⁺P

SUBMITTER: Kwun J 

PROVIDER: S-EPMC5737135 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature