Invariant natural killer T cells in multiple sclerosis

Abstract

Invariant natural killer T (iNKT) cells are a subpopulation of lymphocytes that express both a CD1d-restricted αβ T cell receptor (TCR) and NK cell markers. iNKT cell perturbations are implicated in a wide variety of autoimmune diseases including Multiple Sclerosis (MS). Our results confirmed a significant reduction in the percentage of iNKT cells in MS patients with respect to healthy donors. In order to understand the immunological significance of iNKT cell reduction in MS, we aimed to define iNKT subsets in a cohort of MS patients of different disease types, Clinically Isolated Syndrome patients (CIS) and patients on different treatments by means of multiparameter flow cytometry and TCR analysis. TCR analysis showed that Vα24 CDR3 region is highly conserved between healthy controls and MS patients, while TCR Vβ11 CDR3 region in iNKT cells of MS patients appeared constrained relative to the pool of cells in healthy controls. As activation, differentiation and maturation processes can be involved in the reduced frequency of iNKT cells, we investigated the role of CD25, CD62L, CD69, CD161 and CD195. Initial observation suggested that co-expression of CD25 and CD161 on iNKT cells is significantly higher in MS patients compared to healthy controls, while CD161 alone is decreased, suggesting that a subpopulation of iNKT cells might be acting as “regulatory subsets” in MS. Because many genetic studies have shown that specific killer cell immunoglobulinlike receptor (KIR) family have a strong association with MS, we evaluated the expression of KIR2DL1/S1, KIR2DL2/L3 and KIR3DL1 on iNKT cells. Our results showed that expression of KIR2DL1/S1 and KIR3DL1 is lower in progressive MS patients compared to healthy controls. RRMS untreated patients have lower expression of both KIR2DL2/L3 and KIR3DL1 than patient treated with Natalizumab, while the contrary is true when looking at expression of KIR2DL1/S1. All together our data showed that perturbation of iNKT cells is associated with expression of specific surface receptors, thus defining subsets of iNKT cells that might be related to progression of disease or used as disease markers.