Origin of regulatory T cells with known specificity for antigen

Nat Immunol. 2002 Aug;3(8):756-63. doi: 10.1038/ni816. Epub 2002 Jul 1.

Abstract

T cell receptor agonists can induce the differentiation of regulatory T (T(R)) cells. We report here that the immunoglobulin kappa-controlled expression of an agonist in different cell types correlated with the phenotype of the generated T(R) cells. We found that aberrant expression on thymic stroma yielded predominantly CD4(+)CD25(+) T(R) cells, which--under physiological conditions--may be induced by ectopically expressed organ-specific antigens and thus prevent organ-specific autoimmunity. Expression of the agonist antigen by nonactivated hematopoietic cells produced mostly CD4(+)CD25(-) T(R) cells. This subset can be derived from mature monospecific T cells without "tutoring" by other T cells and can be generated in the absence of a functioning thymus. Suppression of CD4(+) T cell proliferative responses by both CD25(+) and CD25(-) subsets was interleukin 10 (IL-10) independent and was overcome by IL-2. These data suggest that distinct pathways can be exploited to interfere with unwanted immune responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • Epitopes, T-Lymphocyte / immunology*
  • Flow Cytometry
  • Gene Expression Regulation / immunology
  • Hemagglutinins / genetics
  • Hemagglutinins / immunology
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / immunology
  • Ligands
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Mice, Transgenic
  • Phenotype
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Interleukin-2 / genetics
  • Receptors, Interleukin-2 / immunology
  • Specific Pathogen-Free Organisms
  • T-Lymphocytes / immunology*
  • Thymus Gland / cytology
  • Thymus Gland / immunology

Substances

  • Epitopes, T-Lymphocyte
  • Hemagglutinins
  • Ligands
  • Receptors, Antigen, T-Cell
  • Receptors, Interleukin-2