Role of MHC class II expressing CD4+ T cells in proteolipid protein91-110-induced EAE in HLA-DR3 transgenic mice

Ashutosh Mangalam, Moses Rodriguez, Chella David

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

MHC class II molecules play a central role in the control of adaptive immune responses through selection of the CD4+ T cell repertoire in the thymus and antigen presentation in the periphery. Inherited susceptibility to autoimmune disorders such as multiple sclerosis, rheumatoid arthritis and IDDM are associated with particular MHC class II alleles. Advent of HLA transgenic mice has helped us in deciphering the role of particular HLA DR and DQ class II molecules in human autoimmune diseases. In mice, the expression of class II is restricted to professional antigen-presenting cells (APC). However, in humans, class II is also expressed on T cells, unlike murine T cells. We have developed new humanized HLA class II transgenic mice expressing class II molecules not only on APC but also on a subset of CD4+ Tcells. The expression of class II on CD4+ Tcells is inducible, and class II+ CD4+ Tcells can present antigen in the absence of APC. Further, using EAE, a well-established animal model of MS, we tested the functional significance of these class II+ CD4+ Tcells. DR3.AEo transgenic mice were susceptible to proteolipid protein91-110-induced EAE and showed CNS pathology accompanied by widespread inflammation and demyelination seen in human MS patients, suggesting a role for class II+ CD4+ T cells in the pathogenesis.

Original languageEnglish (US)
Pages (from-to)3356-3370
Number of pages15
JournalEuropean Journal of Immunology
Volume36
Issue number12
DOIs
StatePublished - Dec 1 2006

Keywords

  • EAE/MS
  • Epitopes
  • MHC
  • Neuroimmunology
  • Transgenic

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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