Antigen-specific effector CD4 T lymphocytes school lamina propria dendritic cells to transfer innate tolerance

Jason A. Cascio, Cara L. Haymaker, Rohit D. Divekar, Sarah Zaghouani, Marie Therese Khairallah, Xiaoxiao Wan, Linda M. Rowland, Mermagya Dhakal, Weirong Chen, Habib Zaghouani

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Dendritic cells (DCs) have been shown to play a major role in oral tolerance, and this function has been associated with their ability to produce anti-inflammatory cytokines and to induce suppressive regulatory T cells. In this study, we demonstrate that upon oral administration of Ag, lamina propia (LP) DCs engage specific T cells and acquire a novel mechanism by which they transfer tolerance against diverse T cell specificities. Indeed, when Ig-myelin oligodendrocyte glycoprotein (MOG) carrying the MOG35-55 epitope was orally administered into either T cell-sufficient or -deficient mice, only the T cell-sufficient hosts yielded CD8α+ and CD8α- LP DCs that were able to transfer tolerance to a variety of MHC class II-restricted effector T cells. Surprisingly, these LP DCs upregulated programmed cell death ligand 1 during the initial interaction with MOG-specific T cells and used this inhibitory molecule to suppress activation of T cells regardless of Ag specificity. Furthermore, oral Ig-MOG was able to overcome experimental autoimmune encephalomyelitis induced with CNS homogenate, indicating that the DCs are able to modulate disease involving diverse T cell specificities. This previously unrecognized attribute potentiates DCs against autoimmunity.

Original languageEnglish
Pages (from-to)6004-6014
Number of pages11
JournalJournal of Immunology
Issue number12
StatePublished - Jun 15 2013


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