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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Figure 2

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Phenotype of CD4+CD25+CD69– Tregs. (A) Freshly isolated tonsil T cell su...
Phenotype of CD4+CD25+CD69– Tregs. (A) Freshly isolated tonsil T cell subsets were stained with antibodies to TGF-β1, CTLA-4, CD62 ligand (CD62L), and CD45RA. Stained cells were analyzed by a FACSCalibur. The histograms show representative data, and the graphs show combined data (averages and SEM, n = 3). Mean fluorescent intensity levels for the antigens expressed by the 2 populations are also shown in parentheses. (B) Expression of Foxp3 and GITR by CD4+CD25–CD69+ cells, CD4+CD25+CD69+ cells, CD4+CD25+CD69– Tregs, and CD4+CD25–CD69– T cells, determined by RT-PCR. (C) Foxp3 expression by T cell subsets measured by quantitative real-time RT-PCR. Foxp3 expression was normalized for β-actin levels. Representative data (averages and SD of triplicate measurements) from 4 independent experiments are shown.