Belatacept and CD28 Costimulation Blockade: Preventing and Reducing Alloantibodies over the Long Term
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Purpose of Review
Highlight developments in T and B cell biology that are helping elucidate the mechanisms underlying CD28 pathway blockade-mediated inhibition of alloantibodies in transplantation, and discuss recent clinical observations on the impact of belatacept on de novo and established HLA antibodies.
The identification of T follicular helper cells as the CD4+ T cell subset required for optimal humoral immunity, along with newly identified roles for CD28 and the B7 molecules on B cell lineage cells, has begun to pave the way for improved understanding and discovery of the mechanisms of CD28 costimulation blockade-mediated antibody inhibition. There has been resurgent clinical interest in the ability of belatacept to attenuate alloantibody responses. New reports have continued to document its ability to prevent de novo antibody responses, and more recent studies have surfaced exploring its potential to control nascent or pre-existing HLA antibodies.
A growing understanding of the mechanisms of anti-CD28-mediated alloantibody inhibition and continued clinical successes will guide the clinical optimization of belatacept and next-generation CD28 blockers to prevent and reduce alloantibodies over the long term.
KeywordsBelatacept Alloantibodies Costimulation blockade Kidney transplantation CD28 pathway CTLA-4-Ig
Compliance with Ethical Standards
Conflict of Interest
Raul Badell reports grants from NIH/NIAID (K08 AI132747) during the conduct of the study. Ronald F. Parsons, Christian P. Larsen, and Thomas C. Pearson declare no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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