Mesenchymal Stem Cells Differentially Modulate Effector CD8+ T Cell Subsets and Exacerbate Experimental Autoimmune Encephalomyelitis. (October 2014)

• Record Type: Journal Article
• Authors: Glenn, Justin D.; Smith, Matthew D.; Calabresi, Peter A.; Whartenby, Katharine A.
• Is Part Of: Stem cells. Volume 32:Number 10(2014:Oct.)
• Page Start: 2744
• Page End: 2755
• Publication Date: 2014-10
• Subjects: Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.1755
• Languages: English
• ISSNs: 1066-5099

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <p>Mesenchymal stem cells (MSC) have emerged as a promising candidate for inflammatory suppression and disease amelioration, especially of neuro‐inflammatory diseases such as multiple sclerosis (MS). Auto‐reactive CD4+ and CD8+ T cells acquire pathogenic IFNγ‐producing‐ (Type I) and IL‐17A‐producing‐ (Type 17) effector phenotypes in MS and its animal model experimental autoimmune encephalomyelitis (EAE). Although MSC have been extensively demonstrated to suppress pathogenic effector CD4+ T cells and CD4+ T cell‐mediated EAE, surprisingly few studies have addressed their modulation of effector CD8+ T cells represented in MS or their impact on CD8+ T cell‐mediated EAE. We find that MSC differentially modulate CD8+ T cell development depending on effector T cell subtype. MSC drive activated low‐IFNγ producers toward an enhanced high‐IFNγ Tc1‐like phenotype but strongly inhibit the production of IL‐17A and Tc17 polarization in vitro. These observations are underscored by differential MSC modulation of T cell activation, proliferation, and signature transcription factor up‐regulation. In addition, effector CD8+ T cells co‐cultured with MSC exhibited increased production of IL‐2, a molecule known to enhance IFNγ, yet suppress IL‐17A, production. Based on these in vitro effects on CD8+ T cells, we next evaluated their impact on the severity of EAE. To better evaluate CD8+ T cells, we immunized mice with MOG<sub>37‐50</sub>, which is a CD8‐targeted epitope. Our results revealed a worsening of disease, consistent with their in vitro stimulation of Tc1 cells. These findings highlight the emerging duality of MSC in immune modulation and provide implications for their future use in immune‐related diseases. S<sc>tem</sc> C<sc>ells</sc><italic>2014;32:2744–2755</italic></p> </abstract>