Integrin antagonists prevent costimulatory blockade-resistant transplant rejection by CD8(+) memory T cells.

ABSTRACT: The success of belatacept in late-stage clinical trials inaugurates the arrival of a new class of immunosuppressants based on costimulatory blockade, an immunosuppression strategy that disrupts essential signals required for alloreactive T-cell activation. Despite having improved renal function, kidney transplant recipients treated with belatacept experienced increased rates of acute rejection. This finding has renewed focus on costimulatory blockade-resistant rejection and specifically the role of alloreactive memory T cells in mediating this resistance. To study the mechanisms of costimulatory blockade-resistant rejection and enhance the clinical efficacy of costimulatory blockade, we developed an experimental transplant system that models a donor-specific memory CD8(+) T-cell response.

SUBMITTER: Kitchens WH 

PROVIDER: S-EPMC3467016 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature