Journal article
The disease-ameliorating function of autoregulatory CD8 T cells is mediated by targeting of encephalitogenic CD4 T cells in experimental autoimmune encephalomyelitis
The Journal of immunology (1950), Vol.191(1), pp.117-126
07/01/2013
DOI: 10.4049/jimmunol.1300452
PMCID: PMC3691355
PMID: 23733879
Abstract
Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the CNS, and CD8 T cells are the predominant T cell population in MS lesions. Given that transfer of CNS-specific CD8 T cells results in an attenuated clinical demyelinating disease in C57BL/6 mice with immunization-induced experimental autoimmune encephalomyelitis (EAE), we investigated the cellular targets and mechanisms of autoreactive regulatory CD8 T cells. In this study we report that myelin oligodendrocyte glycoprotein peptide (MOG35-55)-induced CD8 T cells could also attenuate adoptively transferred, CD4 T cell-mediated EAE. Whereas CD8(-/-) mice exhibited more severe EAE associated with increased autoreactivity and inflammatory cytokine production by myelin-specific CD4 T cells, this was reversed by adoptive transfer of MOG-specific CD8 T cells. These autoregulatory CD8 T cells required in vivo MHC class Ia (K(b)D(b)) presentation. Interestingly, MOG-specific CD8 T cells could also suppress adoptively induced disease using wild-type MOG35-55-specific CD4 T cells transferred into K(b)D(b-/-) recipient mice, suggesting direct targeting of encephalitogenic CD4 T cells. In vivo trafficking analysis revealed that autoregulatory CD8 T cells are dependent on neuroinflammation for CNS infiltration, and their suppression/cytotoxicity of MOG-specific CD4 T cells is observed both in the periphery and in the CNS. These studies provide important insights into the mechanism of disease suppression mediated by autoreactive CD8 T cells in EAE.
Details
- Title: Subtitle
- The disease-ameliorating function of autoregulatory CD8 T cells is mediated by targeting of encephalitogenic CD4 T cells in experimental autoimmune encephalomyelitis
- Creators
- Sterling B Ortega - Department of Pathology, University of Texas Southwestern Medical Center, Dallas TX 75390, USAVenkatesh P KashiAndrew F TylerKhrishen CunnusamyJason P MendozaNitin J Karandikar
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.191(1), pp.117-126
- DOI
- 10.4049/jimmunol.1300452
- PMID
- 23733879
- PMCID
- PMC3691355
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Publisher
- United States
- Grant note
- R01 AI065463 / NIAID NIH HHS K24 AI079272 / NIAID NIH HHS R01 AI092106 / NIAID NIH HHS R01 AI053439 / NIAID NIH HHS
- Language
- English
- Date published
- 07/01/2013
- Academic Unit
- Pathology
- Record Identifier
- 9984047734302771
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