B cells and professional APCs recruit regulatory T cells via CCL4.

Publisher: Nature America Inc Country of Publication: United States NLM ID: 100941354 Publication Model: Print Cited Medium: Print ISSN: 1529-2908 (Print) Linking ISSN: 15292908 NLM ISO Abbreviation: Nat Immunol Subsets: MEDLINE

Original Publication: New York, NY : Nature America Inc. c2000-

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

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.

MC_U105184296 United Kingdom MRC_ Medical Research Council

0 (Autoantibodies)
0 (Chemokine CCL4)
0 (Chemokines)
0 (Macrophage Inflammatory Proteins)
0 (RNA, Messenger)
0 (Receptors, Interleukin-2)

Date Created: 20011110 Date Completed: 20011228 Latest Revision: 20220414

20250114

10.1038/ni735

11702067