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A CD40 targeting peptide prevents severe symptoms in experimental autoimmune encephalomyelitis.

ABSTRACT: CD40/CD154-interaction is critical in the development of Experimental Autoimmune Encephalomyelitis (EAE; mouse model of Multiple Sclerosis). Culprit CD4+CD40+ T cells drive a more severe form of EAE than conventional CD4 T cells. Blocking CD40/CD154-interaction with CD154-antibody prevents or ameliorates disease but had thrombotic complications in clinical trials. We targeted CD40 using a CD154-sequence based peptide. Peptides in human therapeutics demonstrate good safety. A small peptide, KGYY6, ameliorates EAE when given as pretreatment or at first symptoms. KGYY6 binds Th40 and memory T cells, affecting expression of CD69 and IL-10 in the CD4 T cell compartment, ultimately hampering disease development.

SUBMITTER: Vaitaitis GM

PROVIDER: S-EPMC6535109 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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A CD40 targeting peptide prevents severe symptoms in experimental autoimmune encephalomyelitis.

Vaitaitis Gisela M GM Yussman Martin G MG Wagner David H DH

Journal of neuroimmunology 20190321

CD40/CD154-interaction is critical in the development of Experimental Autoimmune Encephalomyelitis (EAE; mouse model of Multiple Sclerosis). Culprit CD4<sup>+</sup>CD40<sup>+</sup> T cells drive a more severe form of EAE than conventional CD4 T cells. Blocking CD40/CD154-interaction with CD154-antibody prevents or ameliorates disease but had thrombotic complications in clinical trials. We targeted CD40 using a CD154-sequence based peptide. Peptides in human therapeutics demonstrate good safety. ...[more]

PMID: 30925295

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