Regulatory T cells can migrate to follicles upon T cell activation and suppress GC-Th cells and GC-Th cell–driven B cell responses
Hyung W. Lim, … , Peter Hillsamer, Chang H. Kim
Hyung W. Lim, … , Peter Hillsamer, Chang H. Kim
Published December 1, 2004
Citation Information: J Clin Invest. 2004;114(11):1640-1649. https://doi.org/10.1172/JCI22325.
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Article Immunology

Regulatory T cells can migrate to follicles upon T cell activation and suppress GC-Th cells and GC-Th cell–driven B cell responses

Abstract

How Tregs migrate to GCs, and whether they regulate the helper activity of the T cells in GCs (GC-Th cells) remains poorly understood. We found a T cell subset in human tonsils that displays potent suppressive activities toward GC-Th cell–dependent B cell responses. These Tregs with the surface phenotype of CD4+CD25+CD69– migrate well to CCL19, a chemokine expressed in the T cell zone, but poorly to CXCL13, a chemokine expressed in the B cell zone. This migration toward the T cell–rich zone rapidly changes to trafficking toward B cell follicles upon T cell activation. This change in chemotactic behavior upon activation of T cells is consistent with their switch in the expression of the 2 chemokine receptors CXCR5 and CCR7. CD4+CD25+CD69– Tregs suppress GC-Th cells and GC-Th cell–induced B cell responses such as Ig production, survival, and expression of activation-induced cytosine deaminase. Our results have identified a subset of Tregs that is physiologically relevant to GC-Th cell–dependent B cell responses and a potential regulation mechanism for the trafficking of these Tregs to GCs.

Authors

Hyung W. Lim, Peter Hillsamer, Chang H. Kim

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CD4+CD25+CD69– Tregs suppress GC-B cell survival and GC-Th cell_induced ...
CD4+CD25+CD69– Tregs suppress GC-B cell survival and GC-Th cell_induced AID expression. (A) CD4+CD25+CD69– Tregs suppress CD57+ GC-Th cell_dependent GC-B cell survival. CD4+CD25+CD69– Tregs were cultured along with 105 (×1) CD57+ GC-Th cells and GC-B cells for 5 days. Live B cells (CD19+CD4– cells), acquired by a FACSCalibur for 100 seconds after culture, are shown as dot plots. One set of representative dot plot data from 3 independent experiments is shown. *Significant differences from the cultures of GC-B and GC-Th cells in 3 independent experiments. (B and C) CD4+CD25+CD69– Tregs suppress the expression of AID induced by CD57+ GC-Th cells. Indicated numbers of CD4+CD25+CD69– Tregs were cultured for 5 days with 0.5 × 106 (×1) CD57+ GC-Th cells and 0.5 × 106 naive (NV) B cells. Cultured cells were harvested and examined for the expression of AID and β-actin by RT-PCR. A representative set of data from 3 independent experiments is shown in B, and combined data (averages and SEM) in graph form are shown in C.