Cutting edge: in vitro-generated tolerogenic APC induce CD8+ T regulatory cells that can suppress ongoing experimental autoimmune encephalomyelitis

J Immunol. 2004 Feb 15;172(4):1991-5. doi: 10.4049/jimmunol.172.4.1991.

Abstract

APC exposed to TGFbeta2 and Ag (tolerogenic APC) promote peripheral Ag-specific tolerance via the induction of CD8(+) T regulatory cells capable of suppressing Th1 and Th2 immunity. We postulated that tolerogenic APC might reinstate tolerance toward self-neuronal Ags and ameliorate ongoing experimental autoimmune encephalomyelitis (EAE). Seven days after immunization with myelin basic protein (MBP), mice received MBP-specific tolerogenic APC, and EAE was evaluated clinically. To test for the presence and the phenotype of T regulatory cells, CD4 and/or CD8 T cells from tolerogenic APC-treated mice were transferred to naive mice before their immunization with MBP. The MBP-specific tolerogenic APC decreased both the severity and incidence of ongoing EAE. Tolerance to self-neuronal Ags was induced in naive recipient mice via adoptive transfer of CD8(+), but not CD4(+) T cells. Rational use of in vitro-generated tolerogenic APC may lead to novel therapy for autoimmune disease.

Publication types

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

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology*
  • Antigen-Presenting Cells / transplantation
  • Autoantigens / administration & dosage
  • Autoantigens / immunology
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / prevention & control*
  • Female
  • Immune Tolerance*
  • Injections, Intravenous
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Myelin Basic Protein / administration & dosage
  • Myelin Basic Protein / immunology
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / immunology*
  • Transforming Growth Factor beta / pharmacology
  • Transforming Growth Factor beta2

Substances

  • Autoantigens
  • Myelin Basic Protein
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta2