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
View: Text | PDF | Erratum
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

×

Figure 6

Options: View larger image (or click on image) Download as PowerPoint
CD4+CD25+CD69– Tregs are found in the IFAs and GCs of tonsils. To measur...
CD4+CD25+CD69– Tregs are found in the IFAs and GCs of tonsils. To measure distribution of CD4+CD25+CD69– Tregs, frozen tonsil sections were stained for CD4, CD25, and CD69 (A and B). Secondary follicles with GCs were identified by staining of serial sections with antibodies for CD57, IgD, and CD4 (not shown). Stained sections were analyzed with a confocal microscopy system (Bio-Rad Laboratories Inc. MRC-1024UV microscope, and Nikon Inc. Diaphot 300 microscope). A representative set of data from 5 independent experiments using 3 different tonsil specimens is shown. Arrows indicate CD4+CD25+CD69– Tregs, and the circled cells are CD4+CD25+CD69+ T cells.