Circulating MAIT cells in multiple sclerosis and amyotrophic lateral sclerosis

Abstract

Neurological disorders, including multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS), may be associated with alterations in blood cell composition and phenotype. Here, we focused our attention on circulating mucosal-associated invariant T (MAIT) cells, a CD8⁺ T cell memory population expressing the invariant Vα7.2 region in the T cell receptor and high surface levels of the CD161 marker. Transcriptomics data relative to peripheral blood mononuclear cells (PBMC) highlighted downregulation of CD161 and other MAIT-associated markers in progressive MS and not relapsing remitting (RR)-MS when gene expressions relative to each disease course were compared to those from healthy controls. Multiparametric flow cytometry of freshly isolated PBMC samples from untreated RR-MS, primary or secondary progressive MS (PP- or SP-MS), ALS and age- and sex-matched healthy controls revealed specific loss of circulating CD8⁺ MAIT cells in PP-MS and no other MS courses or another neurological disorder such as ALS. Overall, these observations point to the existence of immunological changes in blood specific for the primary progressive course of MS that may support clinical definition of disease.

Keywords: CD161; MAIT cells; amyotrophic lateral sclerosis; blood; progressive multiple sclerosis.

Figure 1

CD161 gene mRNA levels are down-regulated in progressive MS. CD161 gene transcript levels (reported in Log2 expression) were evaluated in PBMCs from 40 healthy controls (HC), 23 PP-MS, 21 SP-MS and 52 RR-MS patients. Group comparisons were evaluated by unpaired t-test with Welch’s correction in case of unequal variances. * p<0.05, *** p<0.001.

Figure 2

Circulating MAIT cells are reduced in primary progressive MS and no other MS forms or ALS. The frequencies of CD161^high and CD161^highVα7.2⁺ MAIT cells among total CD8⁺ T cells and the respective central memory (T_CM, CD45⁺CCR7⁺), effector memory (T_EM, CD45RO⁺CCR7^-) and naïve (CD45RO^-) subsets, were evaluated by multiparametric flow cytometry in 26 RR-MS (mean age 39.81), 19 PP-MS (mean age: 53.61), 14 SP-MS (mean age: 53.93) and 21 ALS patients (mean age: 58.19) (black circles) and compared to age- and sex-matched healthy controls (grey circles) (A, B). Group comparisons were evaluated by unpaired t-test with Welch’s correction in case of unequal variances or Mann-Whitney test in case of non-normal distribution. * p<0.05, ** p<0.01, *** p<0.001.