Loss of Circulating CD8+ CD161high T Cells in Primary Progressive Multiple Sclerosis

Massimo Acquaviva; Claudia Bassani; Nicole Sarno; Gloria Dalla Costa; Marzia Romeo; Francesca Sangalli; Bruno Colombo; Lucia Moiola; Vittorio Martinelli; Giancarlo Comi; Cinthia Farina

doi:10.3389/fimmu.2019.01922

Loss of Circulating CD8+ CD161^high T Cells in Primary Progressive Multiple Sclerosis

Front Immunol. 2019 Aug 14:10:1922. doi: 10.3389/fimmu.2019.01922. eCollection 2019.

Affiliation

¹ Division of Neuroscience, Institute of Experimental Neurology, San Raffaele Scientific Institute, Milan, Italy.

Abstract

Recent evidence suggests that the primary progressive form of multiple sclerosis (PP-MS) may present with specific immunological alterations. In this study we focused our attention on CD161, an NK and T cell marker upregulated in relapsing-remitting MS, and investigated its transcript and protein levels in blood cells from PP-MS and healthy individuals. We demonstrated transcriptional downregulation of CD161 in PP-MS and described concomitant mRNA reduction for RORgt, CCR6, CXCR6, KLRK1/NKG2D and many other markers typical of mucosa associated invariant T (MAIT) cells. Targeted multiparametric flow cytometry on fresh blood cells from an independent cohort of case-control subjects confirmed the selective loss of circulating CD8 CD161^high T cells, which consist mainly of MAIT cells, and not of CD8 CD161^int T cells in PP-MS. These data demonstrate alterations in a specific circulating immune cell subset in MS patients with progressive onset.

Keywords: CD161; CD8; MAIT cells; blood; progressive multiple sclerosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
CD8-Positive T-Lymphocytes / immunology*
CD8-Positive T-Lymphocytes / metabolism
Cohort Studies
Female
Gene Expression Profiling / methods
Humans
Male
Middle Aged
Mucosal-Associated Invariant T Cells / immunology*
Mucosal-Associated Invariant T Cells / metabolism
Multiple Sclerosis, Chronic Progressive / blood
Multiple Sclerosis, Chronic Progressive / genetics
Multiple Sclerosis, Chronic Progressive / immunology*
NK Cell Lectin-Like Receptor Subfamily B / genetics
NK Cell Lectin-Like Receptor Subfamily B / immunology*
NK Cell Lectin-Like Receptor Subfamily B / metabolism
NK Cell Lectin-Like Receptor Subfamily K / genetics
NK Cell Lectin-Like Receptor Subfamily K / immunology
NK Cell Lectin-Like Receptor Subfamily K / metabolism
Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
Nuclear Receptor Subfamily 1, Group F, Member 3 / immunology
Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
Receptors, CCR6 / genetics
Receptors, CCR6 / immunology
Receptors, CCR6 / metabolism
Receptors, CXCR6 / genetics
Receptors, CXCR6 / immunology
Receptors, CXCR6 / metabolism

Substances

CCR6 protein, human
CXCR6 protein, human
KLRK1 protein, human
NK Cell Lectin-Like Receptor Subfamily B
NK Cell Lectin-Like Receptor Subfamily K
Nuclear Receptor Subfamily 1, Group F, Member 3
RORC protein, human
Receptors, CCR6
Receptors, CXCR6