Early activation of CD4+ and CD8+ T lymphocytes by myelin basic protein in subjects with MS.

Borros Arneth

doi:10.1186/s12967-015-0715-6

Abstract

BackgroundMultiple sclerosis is the most common autoimmune disorder affecting the central nervous system. In this study, whole blood samples were analyzed for activation capacity and the activatability of CD4+ and CD8+ T-lymphocytes by human total myelin basic protein (MBP), human MBP 104–118 fragment, and guinea pig MBP 68–82 fragment.MethodsWhole blood samples from healthy human subjects were compared with samples from patients with multiple sclerosis (MS). In particular, the expression of CD69, a surface marker of T-lymphocyte activity, was measured via flow cytometry before and after 14 h of incubation with human total MBP, MBP 104–118 fragment and/or guinea pig MBP 68–82 fragment. The results were compared between 15 patients with MS and 15 healthy subjects.ResultsIn response to all three MBP forms, CD4+ and CD8+ T-lymphocytes from patients with MS demonstrated greater activatability than those from healthy subjects. These results indicate that in patients with MS, latent pre-activation to MBP epitopes results in an increased activation capacity of T-lymphocytes.ConclusionThis effect may occur because immunization against MBP (at least in a subset of patients) plays a pathophysiological role in MS pathogenesis. Alternatively, this result may represent a non-specific, bystander autoimmune phenomenon.

Highlights

Multiple sclerosis is the most common autoimmune disorder affecting the central nervous system
There was no significant difference between the numbers of activated CD4+ and/or CD8+ T-lymphocytes
The results presented here demonstrate that T-lymphocytes from patients with multiple sclerosis (MS) respond very differently to myelin basic protein (MBP) compared with T-lymphocytes from healthy subjects

Summary

Introduction

Multiple sclerosis is the most common autoimmune disorder affecting the central nervous system. The symptoms of multiple sclerosis (MS) are considered to represent signs of an autoimmune disease [1]. MS is a human disease that is closely related to the animal model of experimental autoimmune encephalitis (EAE) [4]. In this animal model, mice are immunized by an injection of myelin basic protein (MBP) and subsequently develop an MS-like relapsing disease pattern. Immunization against human MBP is associated with the occurrence of pre-activated T-lymphocytes specific to MBP, and several authors have described immune reactions and autoimmune diseases as consequences of T-lymphocytes remaining from former immunizations [4–7]

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Discussion

Conclusion