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

J Transl Med. 2015 Nov 2:13:341. doi: 10.1186/s12967-015-0715-6.

Abstract

Background: Multiple 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.

Methods: Whole 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.

Results: In 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.

Conclusion: This 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.

MeSH terms

  • Adult
  • Animals
  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • CD4-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / cytology*
  • Case-Control Studies
  • Cell Separation
  • Epitopes / chemistry
  • Erythrocytes / cytology
  • Female
  • Flow Cytometry
  • Guinea Pigs
  • Humans
  • Lectins, C-Type / metabolism
  • Lymphocyte Activation*
  • Male
  • Multiple Sclerosis / blood*
  • Multiple Sclerosis / immunology
  • Myelin Basic Protein / blood*

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • Epitopes
  • Lectins, C-Type
  • MBP protein, human
  • Myelin Basic Protein