Invariant natural killer T cells in multiple sclerosis
File(s)
Author(s)
Kamel, Fatemah Omar
Type
Thesis
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.
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.
Version
Open Access
Date Issued
2013-05
Date Awarded
2013-10
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Boyton, Rosemary
Altmann, Danny
Nicholas, Richard
Sponsor
Saudi Arabia. Royal Embassy (UK)
Publisher Department
Medicine
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)