Enhanced tolerance to autoimmune uveitis in CD200-deficient mice correlates with a pronounced Th2 switch in response to antigen challenge

N. Taylor, K. McConnachie, C. J. Calder, Rosemary Anne Dawson, A. D. Dick, J. D. Sedgwick, Janet Mary Liversidge

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

A single exposure to inhaled Ag 10 days before immunization leads to long term, Ag-specitie tolerance. Respiratory tract myeloid APCs are implicated, but how regulation is invoked, and how tolerance is sustained are unclear. This study examines the in vivo function of the myeloid regulatory molecule CD200 in the process of tolerance induction. Despite earlier onset of experimental autoimmune uveitis in sham-tolerized, CD200-deficient mice, disease incidence and subsequent severity were actually reduced compared with those in wild-type mice. Protection was more effective and long term, lasting at least 28 days. Halting disease progression and tolerance in CD200(-/-) mice correlated with a marked increase in Th2-associated cytokine production by Ag-challenged splenocytes. Reduced overall disease and enhanced tolerance in the CD200-deficient mice in this model system were unexpected and may be related to altered populations of MHC class IIlow APC in the respiratory tract compared with wild-type mice together with associated activation of STAT6 in draining lymph nodes of tolerized mice. These data indicate that in the absence of default inhibitory CD200 receptor signaling, alternative, powerful regulatory mechanisms are invoked. This may represent either permissive dominant Th2 activation or an altered hierarchy of negative signaling by other myeloid cell-expressed regulatory molecules.

Original languageEnglish
Pages (from-to)143-154
Number of pages11
JournalThe Journal of Immunology
Volume174
Issue number1
Publication statusPublished - Jan 2005

Keywords

  • REGULATORY T-CELLS
  • DENDRITIC CELLS
  • ALTERNATIVE ACTIVATION
  • CUTTING EDGE
  • RESPIRATORY-TRACT
  • INDUCED ARTHRITIS
  • EFFECTOR FUNCTION
  • OX2 GLYCOPROTEIN
  • MYELOID CELLS
  • IN-VITRO

Cite this

Taylor, N., McConnachie, K., Calder, C. J., Dawson, R. A., Dick, A. D., Sedgwick, J. D., & Liversidge, J. M. (2005). Enhanced tolerance to autoimmune uveitis in CD200-deficient mice correlates with a pronounced Th2 switch in response to antigen challenge. The Journal of Immunology, 174(1), 143-154.