Selective blockade of CD28-mediated T cell costimulation protects rhesus monkeys against acute fatal experimental autoimmune encephalomyelitis

Krista G. Haanstra, Karin Dijkman, Noun Bashir, Jan Bauer, Caroline Mary, Nicolas Poirier, Paul Baker, Linda Scobie, Bert A. ’t Hart, Bernard Vanhove

Research output: Contribution to journalArticlepeer-review

Abstract

Costimulatory and coinhibitory receptor–ligand pairs on T cells and APC control the immune response. We have investigated whether selective blockade of CD28–CD80/86 costimulatory interactions, which preserves the coinhibitory CTLA4–CD80/86 interactions and the function of regulatory T (Treg) cells, abrogates the induction of experimental autoimmune encephalomyelitis (EAE) in rhesus monkeys. EAE was induced by intracutaneous immunization with recombinant human myelin oligodendrocyte glycoprotein (rhMOG) in CFA on day 0. FR104 is a monovalent, PEGylated-humanized Fab' Ab fragment against human CD28, cross-reactive with rhesus monkey CD28. FR104 or placebo was administered on days 0, 7, 14, and 21. FR104 levels remained high until the end of the study (day 42). Placebo-treated animals all developed clinical EAE between days 12 and 27. FR104-treated animals did not develop clinical EAE and were sacrificed at the end of the study resulting in a significantly prolonged survival.
Original languageEnglish
Pages (from-to)1454-1466
Number of pages13
JournalJournal of Immunology
Volume194
Issue number4
Early online date14 Jan 2015
DOIs
Publication statusPublished - Feb 2015

Keywords

  • encephalomyelitis
  • immunology
  • autoimmune

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