Edinburgh Research Explorer

Adjuvant immunotherapy of experimental autoimmune encephalomyelitis: immature myeloid cells expressing CXCL10 and CXCL16 attract CXCR3+CXCR6+ and myelin-specific T cells to the draining lymph nodes rather than the central nervous system

Research output: Contribution to journalArticle

Related Edinburgh Organisations

Original languageEnglish
Pages (from-to)2093-101
Number of pages9
JournalJournal of Immunology
Volume188
Issue number5
DOIs
Publication statusPublished - 2012

Abstract

CFA is a strong adjuvant capable of stimulating cellular immune responses. Paradoxically, adjuvant immunotherapy by prior exposure to CFA or live mycobacteria suppresses the severity of experimental autoimmune encephalomyelitis (EAE) and spontaneous diabetes in rodents. In this study, we investigated immune responses during adjuvant immunotherapy of EAE. Induction of EAE in CFA-pretreated mice resulted in a rapid influx into the draining lymph nodes (dLNs) of large numbers of CD11b(+)Gr-1(+) myeloid cells, consisting of immature cells with ring-shaped nuclei, macrophages, and neutrophils. Concurrently, a population of mycobacteria-specific IFN-γ-producing T cells appeared in the dLNs. Immature myeloid cells in dLNs expressed the chemokines CXCL10 and CXCL16 in an IFN-γ-dependent manner. Subsequently, CD4(+) T cells coexpressing the cognate chemokine receptors CXCR3 and CXCR6 and myelin oligodendrocyte glycoprotein (MOG)-specific CD4(+) T cells accumulated within the chemokine-expressing dLNs, rather than within the CNS. Migration of CD4(+) T cells toward dLN cells was abolished by depleting the CD11b(+) cells and was also mediated by the CD11b(+) cells alone. In addition to altering the distribution of MOG-specific T cells, adjuvant treatment suppressed development of MOG-specific IL-17. Thus, adjuvant immunotherapy of EAE requires IFN-γ, which suppresses development of the Th17 response, and diverts autoreactive T cells away from the CNS toward immature myeloid cells expressing CXCL10 and CXCL16 in the lymph nodes.

    Research areas

  • Animals, Cell Differentiation/immunology, Cell Migration Inhibition/immunology, Chemokine CXCL10, Chemokine CXCL6, Encephalomyelitis, Autoimmune, Experimental, Female, Freund's Adjuvant, Interferon-gamma/physiology, Interferon-gamma/therapeutic use, Lymph Nodes, Mice, Mice, Inbred C57BL, Mice, Knockout, Mycobacterium tuberculosis/immunology, Myelin Proteins/immunology, Myelin-Oligodendrocyte Glycoprotein, Myeloid Cells, Receptors, CXCR, Receptors, CXCR3, T-Lymphocyte Subsets

ID: 3572797