An autoimmunity odyssey: how autoreactive T cells infiltrate into the CNS

Immunol Rev. 2012 Jul;248(1):140-55. doi: 10.1111/j.1600-065X.2012.01133.x.

Abstract

Experimental autoimmune encephalomyelitis (EAE) is a widely used animal model of multiple sclerosis (MS), a human autoimmune disease. To explore how EAE and ultimately MS is induced, autoantigen-specific T cells were established, were labeled with fluorescent protein by retroviral gene transfer, and were tracked in vivo after adoptive transfer. Intravital imaging with two-photon microscopy was used to record the entire entry process of autoreactive T cells into the CNS: a small number of T cells first appear in the CNS leptomeninges before onset of EAE, and crawl on the intraluminal surface of blood vessels, which is integrin α4 and αL dependent. After extravasation, the T cells continue into the perivascular space, meeting local antigen-presenting cells (APCs), which present endogenous antigens. This interaction activates the T cells and guides them to penetrate the CNS parenchyma. As the local APCs in the CNS are not saturated with endogenous antigens, exogenous antigens stimulate the autoreactive T cells more strongly and, as a result, exacerbate the clinical outcome. Currently, we are attempting to visualize T-cell activation in vivo in both rat T-cell-mediated EAE and mouse spontaneous EAE models.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigens / immunology
  • Antigens / metabolism
  • Autoimmunity / immunology*
  • Cell Tracking / methods
  • Central Nervous System / immunology*
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Humans
  • Immunologic Memory
  • Mice
  • Multiple Sclerosis / immunology
  • Rats
  • Spleen / immunology
  • Spleen / metabolism
  • T-Lymphocytes / immunology*

Substances

  • Antigens