Autoregulatory CD8+ T cells modulate splenic dendritic cells to inhibit experimental autoimmune encephalomyelitis
Presentation Time: 02:15 PM - 03:30 PM
Poster Board Number: B1002
Abstract ID: 4736
Presenting Author:
Mohit Upadhye , Graduate Research Assistant at Univ. of Iowa Carver Col. of Med.
Abstract:
Experimental Autoimmune Encephalomyelitis (EAE) is the mouse model for multiple sclerosis (MS), an immune-mediated demyelinating disease. We have shown that myelin-reactive CD8+ T cells play a disease-suppressive role in MS/EAE. However, the mechanisms used by these cells are incompletely understood. In this study, we hypothesized that myelin-reactive CD8 T cells inhibit EAE by modulating subsets of splenic dendritic cells (DC). We generated CD8s reactive against PLP178-191 (PLP-CD8) or OVA323-339 (OVA-CD8) as a control, and adoptively transferred them into naïve mice before inducing EAE with PLP178-191. As expected, PLP-CD8 recipients were protected from developing severe EAE. Single-cell transcriptomic analysis of splenic DCs revealed significantly different gene expressions in cDC1 and cDC2 subsets, but not in pDCs. PLP-DC showed upregulation of immunoregulatory and costimulatory genes and enrichment of PD1/PDL1 and chemokine signaling pathways. Flow cytometry confirmed PD-L2 and CD86 elevation in PLP-DCs. Upon TLR stimulation, PLP-DCs produced significantly more IL-10 and less IL-12 than OVA-DCs. PLP-DCs also demonstrated reduced capacity to support CD4 proliferation. Of note, PLP-CD8s directly induced phenotypic changes in PLP-presenting DCs in vitro. These findings highlight the role of CD8-DC crosstalk in immune regulation and suggest that autoregulatory CD8 T cells mediate disease suppression by modulating DCs to become less inflammatory/more tolerogenic.
Autoregulatory CD8+ T cells modulate splenic dendritic cells to inhibit experimental autoimmune encephalomyelitis
Category
Poster and Podium (Block Symposium)