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
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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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Chemotaxis assay. (A) Chemotactic behaviors of CD4+CD25+CD69– Tregs and ...
Chemotaxis assay. (A) Chemotactic behaviors of CD4+CD25+CD69– Tregs and CD4+CD25+CD69+ T cells. (B) CD4+CD25+CD69– Tregs poorly migrate to CCL1. Fresh tonsil mononuclear cells were used as input cells for chemotaxis assays. Indicated chemokines were first titrated to determine optimal concentrations: CXCL13 (4,000 ng/ml), CXCL12 (100 ng/ml), CXCL10 (1,000 ng/ml), CCL19 (2,000 ng/ml), CCL17 (200 ng/ml), CCL4 (100 ng/ml), and CCL1 (500 ng/ml). Cells were allowed to migrate for 3 hours. The migrated cells and input cells were harvested, stained for CD4, CD25, and CD69, and counted by a FACSCalibur. Specific migration after subtraction of the background migration is shown. The background migration rates (percent averages and SEM, 3 experiments) for the 4 subsets were 25 ± 2.6 (CD4+CD25–CD69+), 13.4 ± 4.3 (CD4+CD25+CD69+), 6.1 ± 0.4 (CD4+CD25+CD69– Treg), and 7.2 ± 2 (CD4+CD25–CD69–). The averages and SEM of the data obtained from 3 (A) and 4 (B) independent experiments are shown. *Significant differences between the 2 subsets (A) or from CD4+CD25+CD69– Tregs (B). The P values were 0.048 (CXCL13) and 0.015 (CCL19) in A; and 0.046 (CD25+CD69– Treg vs. CD25+CD69+), 0.007 (CD25+CD69– Treg vs. CD25–CD69+), and 0.03 (CD25+CD69– Treg vs. CD25–CD69–) in B.