Neuroantigen-specific autoregulatory CD8+ T cells inhibit autoimmune demyelination through modulation of dendritic cell function

Venkatesh P. Kashi, Sterling B. Ortega, Nitin J. Karandikar

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Experimental autoimmune encephalomyelitis (EAE) is a well-established murine model of multiple sclerosis, an immune-mediated demyelinating disorder of the central nervous system (CNS). We have previously shown that CNS-specific CD8+ T cells (CNS-CD8+) ameliorate EAE, at least in part through modulation of CNS-specific CD4+ T cell responses. In this study, we show that CNS-CD8 + also modulate the function of CD11c+ dendritic cells (DC), but not other APCs such as CD11b+ monocytes or B220+ B cells. DC from mice receiving either myelin oligodendrocyte glycoprotein-specific CD8+ (MOG-CD8+) or proteolipid protein-specific CD8+ (PLP-CD8+) T cells were rendered inefficient in priming T cell responses from naïve CD4+ T cells (OT-II) or supporting recall responses from CNS-specific CD4+ T cells. CNS-CD8+ did not alter DC subset distribution or MHC class II and CD86 expression, suggesting that DC maturation was not affected. However, the cytokine profile of DC from CNS-CD8+ recipients showed lower IL-12 and higher IL-10 production. These functions were not modulated in the absence of immunization with CD8-cognate antigen, suggesting an antigen-specific mechanism likely requiring CNS-CD8-DC interaction. Interestingly, blockade of IL-10 in vitro rescued CD4+ proliferation and in vivo expression of IL-10 was necessary for the suppression of EAE by MOG-CD8+. These studies demonstrate a complex interplay between CNS-specific CD8+ T cells, DC and pathogenic CD4+ T cells, with important implications for therapeutic interventions in this disease.

Original languageEnglish (US)
Article numbere105763
JournalPLoS One
Volume9
Issue number8
DOIs
StatePublished - Aug 21 2014

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T-cells
Neurology
Demyelinating Diseases
dendritic cells
Dendritic Cells
central nervous system
Central Nervous System
T-lymphocytes
Modulation
T-Lymphocytes
Autoimmune Experimental Encephalomyelitis
encephalitis
interleukin-10
Myelin-Oligodendrocyte Glycoprotein
Interleukin-10
myelin sheath
glycoproteins
CD8 Antigens
antigens
Immunization

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Neuroantigen-specific autoregulatory CD8+ T cells inhibit autoimmune demyelination through modulation of dendritic cell function. / Kashi, Venkatesh P.; Ortega, Sterling B.; Karandikar, Nitin J.

In: PLoS One, Vol. 9, No. 8, e105763, 21.08.2014.

Research output: Contribution to journalArticle

Kashi, Venkatesh P. ; Ortega, Sterling B. ; Karandikar, Nitin J. / Neuroantigen-specific autoregulatory CD8+ T cells inhibit autoimmune demyelination through modulation of dendritic cell function. In: PLoS One. 2014 ; Vol. 9, No. 8.
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