Journal article
A Functionally Distinct CXCR3 + /IFN-γ + /IL-10 + Subset Defines Disease-Suppressive Myelin-Specific CD8 T Cells
The Journal of immunology (1950), Vol.206(6), pp.1151-1160
03/15/2021
DOI: 10.4049/jimmunol.2001143
PMCID: PMC8059448
PMID: 33558376
Abstract
Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the CNS. We have previously demonstrated that CNS-specific CD8 T cells possess a disease-suppressive function in MS and variations of its animal model, experimental autoimmune encephalomyelitis (EAE), including the highly clinically relevant relapsing-remitting EAE disease course. Regulatory CD8 T cell subsets have been identified in EAE and other autoimmune diseases, but studies vary in defining phenotypic properties of these cells. In relapsing-remitting EAE, PLP
CD8 T cells suppress disease, whereas PLP
CD8 T cells lack this function. In this study, we used this model to delineate the unique phenotypic properties of CNS-specific regulatory PLP
CD8 T cells versus nonregulatory PLP
or OVA
CD8 T cells. Using multiparametric flow cytometric analyses of phenotypic marker expression, we identified a CXCR3
subpopulation among activated regulatory CD8 T cells, relative to nonregulatory counterparts. This subset exhibited increased degranulation and IFN-γ and IL-10 coproduction. A similar subset was also identified in C57BL/6 mice within autoregulatory PLP
CD8 T cells but not within nonregulatory OVA
CD8 T cells. This disease-suppressing CD8 T cell subpopulation provides better insights into functional regulatory mechanisms, and targeted enhancement of this subset could represent a novel immunotherapeutic approach for MS.
Details
- Title: Subtitle
- A Functionally Distinct CXCR3 + /IFN-γ + /IL-10 + Subset Defines Disease-Suppressive Myelin-Specific CD8 T Cells
- Creators
- Ashley A Brate - University of IowaAlexander W Boyden - University of IowaIsaac J Jensen - University of IowaVladimir P Badovinac - University of IowaNitin J Karandikar - University of Iowa
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.206(6), pp.1151-1160
- DOI
- 10.4049/jimmunol.2001143
- PMID
- 33558376
- PMCID
- PMC8059448
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Grant note
- R01 AI121567 / NIAID NIH HHS I01 BX003677 / BLRD VA T32 AI007485 / NIAID NIH HHS
- Language
- English
- Date published
- 03/15/2021
- Academic Unit
- Microbiology and Immunology; Pathology
- Record Identifier
- 9984181070402771
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