B cells and professional APCs recruit regulatory T cells via CCL4.
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.
Bystry
R S
RS
Medical Research Council, Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK.
Aluvihare
V
V
Welch
K A
KA
Kallikourdis
M
M
Betz
A G
AG
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology*; D001323:Autoantibodies / Q000096:biosynthesis; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D054407:Chemokine CCL4; D018925:Chemokines / Q000096:biosynthesis; D002634:Chemotaxis, Leukocyte; D020869:Gene Expression Profiling; D018858:Germinal Center / Q000166:cytology; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis; D015375:Receptors, Interleukin-2 / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000145:classification; D015854:Up-Regulation
D001323:Autoantibodies; D054407:Chemokine CCL4; D018925:Chemokines; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2