B cells and professional APCs recruit regulatory T cells via CCL4

Nat Immunol. 2001 Dec;2(12):1126-32. doi: 10.1038/ni735.


Using gene expression profiling, we show here that activation of B cells and professional antigen-presenting cells (APCs) induces the expression of common chemokines. Among these, CCL4 was the most potent chemoattractant of a CD4+CD25+ T cell population, which is a characteristic phenotype of regulatory T cells. Depletion of either regulatory T cells or CCL4 resulted in a deregulated humoral response, which culminated in the production of autoantibodies. This suggested that the recruitment of regulatory T cells to B cells and APCs by CCL4 plays a central role in the normal initiation of T cell and humoral responses, and failure to do this leads to autoimmune activation.

MeSH terms

  • Animals
  • Antigen-Presenting Cells / drug effects
  • Antigen-Presenting Cells / immunology*
  • Autoantibodies / biosynthesis
  • Autoimmunity*
  • B-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Chemokine CCL4
  • Chemokines / biosynthesis
  • Chemotaxis, Leukocyte*
  • Gene Expression Profiling
  • Germinal Center / cytology
  • Immunophenotyping
  • Lymphocyte Activation
  • Lymphocyte Depletion
  • Macrophage Inflammatory Proteins / pharmacology
  • Macrophage Inflammatory Proteins / physiology*
  • Mice
  • RNA, Messenger / biosynthesis
  • Receptors, Interleukin-2 / physiology
  • T-Lymphocyte Subsets / classification
  • Up-Regulation


  • Autoantibodies
  • Chemokine CCL4
  • Chemokines
  • Macrophage Inflammatory Proteins
  • RNA, Messenger
  • Receptors, Interleukin-2