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 switch their expression pattern of chemokine recept...
CD4+CD25+CD69– Tregs switch their expression pattern of chemokine receptors and chemotactic responsiveness upon T cell activation. Tonsil mononuclear cells, freshly isolated or briefly activated for 10_14 hours with phytohemagglutinin (PHA) or for 5_10 hours with anti-CD3 and anti-CD28, were examined for their expression of chemokine receptors (A, B, and D) or for chemotactic responsiveness (C and E). In D, the chemokine receptors were examined by 1- or 2-step staining methods to avoid cross-reaction with the anti-CD3 and anti-CD28 antibodies used to activate the cells; these methods are less sensitive than the 3-step method used for A and B. The data obtained from 3 independent experiments were combined, and averages (and SEM in A) are shown. The background percent migration rates (averages and SEM, 3 experiments) for the 4 cell subsets were 23 ± 4.4 (CD4+CD25–CD69+), 16.3 ± 3.2 (CD4+CD25+CD69+), 23 ± 1.0 (CD4+CD25+CD69– Treg), and 11 ± 3.2 (CD4+CD25–CD69–). *Significant differences between the 2 samples. The P values were 0.024 (a), 0.042 (b), 0.032 (c), 0.019 (d), 0.045 (e), 0.033 (f), 0.041 (g), 0.002 (h), 0.049 (i), 0.021 (j), 0.023 (k), 0.009 (l), 0.004 (m), and 0.006 (n).