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

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

doi:10.3389/fimmu.2019.01922

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 CD161high T cells, which consist mainly of MAIT cells, and not of CD8 CD161int T cells in PP-MS. These data demonstrate alterations in a specific circulating immune cell subset in MS patients with progressive onset.

Highlights

Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system (CNS), presenting with distinct clinical courses [1]
In primary progressive MS we detected a trend to higher frequency of CD161+ CD4 T cells (Mean ± SEM Ctrl vs. primary progressive form of multiple sclerosis (PP-MS) 19.86 ± 1.29 vs. 25.44 ± 2.35, p-value 0.05) that was reproduced in the naïve CD4 T cell population (Mean ± SEM Ctrl vs. PP-MS 3.37 ± 0.49 vs. 9.26 ± 1.97, p-value 0.0041) and an overall lower percentage of CD161 expressing CD8 T cells (Mean ± SEM Ctrl vs. PP-MS 19.85 ± 1.57 vs. PP-MS: 14.82 ± 1.62, p-value 0.046) which was paralleled by 32.5% reduction in the CD161 expressing effector memory CD8 T cell population (Mean ± SEM Ctrl vs. PP-MS 39.92 ± 4.87 vs. 27.08 ± 3.60, p-value 0.043, Figure 1C)
The first observation is the higher frequency of CD161+ naïve CD4 T cells in PP-MS compared to the heathy subjects

Summary

Introduction

Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system (CNS), presenting with distinct clinical courses [1]. The study of the pathogenic processes occurring during experimental neuroinflammation has led to a large repertoire of drugs targeting peripheral immunity, most of which have shown efficacy in treating the relapsing-remitting form of disease but not progressive MS [2]. These observations have led to the hypothesis that the contribution of the immune system to PP-MS is not relevant. The evidence that therapeutic depletion of CD20 positive B lymphocytes can be of benefit in progressive MS [2] has reproposed the need of understanding the immunological alterations associated with this course of disease This information may lay the basis for novel knowledge-driven therapeutic immune checkpoints for each MS stage. As a first step in this direction, we have investigated blood transcriptomics changes in MS and recently demonstrated that peripheral blood mononuclear cells (PBMC) carry important transcriptional information whose monitoring may emphasize

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Conclusion