Abstract
Multiple sclerosis (MS), an autoimmune disease with neurodegeneration and inflammation is characterized by several alterations of different T cell subsets. However, few data exist on the role of iNKT lymphocytes. To identify possible changes in the phenotype of iNKT cells in patients with different clinical forms of MS and find alterations in their polyfunctionality [i.e., ability to produce simultaneously up to four cytokines such as IL-17, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and IL-4]. We studied a total of 165 patients, 91 with a relapsing-remitting form [RR; 31 were treated with interferon (IFN)1a-β, 25 with natalizumab (NAT), 29 with glatiramer acetate; 17 were newly diagnosed RR without treatment, 19 not-active RR without treatment]. Forty-four patients had a progressive MS: 20 primary progressive (PP) and 24 secondary progressive (SP). A total of 55 age- and sex-matched subjects represented healthy controls (CTR). Among fresh peripheral blood mononuclear cells, iNKT cells were identified by flow cytometry. Moreover, the capability of iNKT cells to produce different cytokines (IL-17, TNF-α, IFN-γ, and IL-4) after in vitro stimulation were evaluated in 18 RR (11 treated with NAT and 7 with IFN), 4 PP, 6 SP, and 16 CTR. No main differences were found in iNKT cell phenotype among MS patients with different MS forms or during different treatments. However, the polyfunctional response of iNKT cells showed Th1 and Th17 profiles. This was well evident in patients with SP form, who are characterized by high levels of inflammation and neurodegeneration, and exhibited a sustained increase in the production of Th17 cytokines. Patients treated with NAT displayed lower levels of iNKT cells producing IL-17, TNF-α, and IFN-γ. Our data suggest that the progressive phase of the disease is characterized by permanent iNKT activation and a skewing towards an inflammatory phenotype. Compared to other treatments, NAT was able to modulate iNKT cell function.
Highlights
Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system (CNS)
T cells were identified by positivity for CD3 expression and negativity for CD14 and CD19, markers included into the DUMP channel. iNKT cells were selected according to the presence of a Vα24JαQ TCR chain
Considering the polyfunctionality of these cells, we found that double negative (DN) iNKT cells able to produce IFN-γ and tumor necrosis factor (TNF)-α, but not IL-4 or IL-17, were decreased in patients treated with NAT (Figure 5M)
Summary
Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system (CNS). The relationship between inflammation and neurodegeneration and their contribution to the different phases of the disease remains ambiguous [1]. It is unclear how these two processes are generated and controlled by different components of the immune system. INKT cells belong to the family of innate-like lymphocytes; they are T lymphocytes characterized by the expression of NK cell markers and an invariant alpha chain and represent less than 1% of circulating T lymphocytes [3]. Multiple sclerosis (MS), an autoimmune disease with neurodegeneration and inflammation is characterized by several alterations of different T cell subsets. Few data exist on the role of iNKT lymphocytes
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