Exploiting apoptosis for therapeutic tolerance induction

Daniel R. Getts, Derrick P. McCarthy, Stephen D. Miller*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

68 Scopus citations


Immune tolerance remains the most promising yet elusive strategy for treating immune-mediated diseases. An experimental strategy showing promise in phase 1 clinical studies is the delivery of Ag cross-linked to apoptotic leukocytes using ethylene carbodiimide. This approach originated from demonstration of the profound tolerance-inducing ability of i.v. administered Ag-coupled splenocytes (Ag-SP) in mice, which has been demonstrated to treat T cell-mediated disorders including autoimmunity, allergy, and transplant rejection. Recent studies have defined the intricate interplay between the innate and adaptive immune systems in Ag-SP tolerance induction. Innate mechanisms include scavenger receptor-mediated uptake of Ag-SP by host APCs, Ag representation, and the required upregulation of PD-L1 expression and IL-10 production by splenic marginal zone macrophages leading to Ag-specific T cell regulation via the combined effects of cell-intrinsic anergy and regulatory T cell induction. In this paper, we discuss the history, advantages, current mechanistic understanding, and clinical potential of tolerance induction using apoptotic Ag-coupled apoptotic leukocytes.

Original languageEnglish (US)
Pages (from-to)5341-5346
Number of pages6
JournalJournal of Immunology
Issue number11
StatePublished - Dec 1 2013

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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