Differential effects of myelin basic protein-activated Th1 and Th2 cells on the local immune microenvironment of injured spinal cord

Exp Neurol. 2016 Mar:277:190-201. doi: 10.1016/j.expneurol.2016.01.002. Epub 2016 Jan 7.

Abstract

Myelin basic protein (MBP) activated T cells (MBP-T) play an important role in the damage and repair process of the central nervous system (CNS). However, whether these cells play a beneficial or detrimental role is still a matter of debate. Although some studies showed that MBP-T cells are mainly helper T (Th) cells, their subtypes are still not very clear. One possible explanation for MBP-T immunization leading to conflicting results may be the different subtypes of T cells are responsible for distinct effects. In this study, the Th1 and Th2 type MBP-T cells (MBP-Th1 and -Th2) were polarized in vitro, and their effects on the local immune microenvironment and tissue repair of spinal cord injury (SCI) after adoptive immunization were investigated. In MBP-Th1 cell transferred rats, the high levels of pro-inflammatory cells (Th1 cells and M1 macrophages) and cytokines (IFN-γ, TNF-α, -β, IL-1β) were detected in the injured spinal cord; however, the anti-inflammatory cells (Th2 cells, regulatory T cells, and M2 macrophages) and cytokines (IL-4, -10, and -13) were found in MBP-Th2 cell transferred animals. MBP-Th2 cell transfer resulted in decreased lesion volume, increased myelination of axons, and preservation of neurons. This was accompanied by significant locomotor improvement. These results indicate that MBP-Th2 adoptive transfer has beneficial effects on the injured spinal cord, in which the increased number of Th2 cells may alter the local microenvironment from one primarily populated by Th1 and M1 cells to another dominated by Th2, Treg, and M2 cells and is conducive for SCI repair.

Keywords: Immune microenvironment; Locomotor recovery; Myelin basic protein; Passive immunization; Spinal cord injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Analysis of Variance
  • Animals
  • Cytokines / genetics
  • Cytokines / metabolism
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Macrophages / metabolism
  • Macrophages / pathology
  • Motor Activity / genetics
  • Motor Disorders / etiology
  • Myelin Basic Protein / genetics
  • Myelin Basic Protein / immunology
  • Myelin Basic Protein / metabolism*
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Psychomotor Performance / physiology
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord Injuries / complications
  • Spinal Cord Injuries / pathology*
  • Tetradecanoylphorbol Acetate / analogs & derivatives
  • Tetradecanoylphorbol Acetate / pharmacology
  • Th1 Cells / metabolism*
  • Th2 Cells / metabolism*

Substances

  • Cytokines
  • Myelin Basic Protein
  • RNA, Messenger
  • 4-O-methyl-12-O-tetradecanoylphorbol 13-acetate
  • Nitric Oxide Synthase Type II
  • Tetradecanoylphorbol Acetate