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Critical role of PD-1/PD-L1 pathway in generation and function of follicular regulatory T cells

Cellular & Molecular Immunology volume 10, pages 286–288 (2013)Cite this article

The balance between follicular helper T cells (TFH cells) and follicular regulatory T (Treg) cells (TFR cells) is one of the key factors for the development of humoral immune responses. How the balance is regulated, however, is largely unknown. In a recent issue of Nature Immunology, Sage et al. revealed a critical role of the programmed death-1 (PD-1)/PD-L1 pathway in TFR cell generation and function,1 which provides a novel insight into the mechanisms how TFH and TFR cells regulate antibody production.

Germinal centers (GCs) are sites within lymph nodules, where B lymphocytes rapidly proliferate and differentiate into plasma cells and memory B cells during humoral immune responses. These events are precisely regulated by interactions between cognate B cells, TFH cells, TFR cells and follicular dendritic cells.2,3,4,5 TFH cells are a specialized CD4+ helper subset, which provides help to B cells. TFR cells are a newly identified CD4+ Treg subset in GCs, which downregulates the GC response.6,7 TFH and TFR cells are defined by expression of the CXC-chemokine receptor 5 (CXCR5) which directs them to B-cell follicles in GCs via gradients of the CXC-chemokine ligand 13 (CXCL13).1,2,8 TFH and TFR cells are present not only in lymph nodes but also in peripheral blood. PD-1 is a well-known inhibitory receptor for humoral immune responses9 and can be expressed by T cells, B cells, macrophages and dendritic cells.10 TFR cells express more PD-1 than TFH cells.1 B cells and dendritic cells express the PD-1 ligands, PD-L1 and PD-L2.10

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  1. Department of Microbiology and Immunology, Showa University School of Medicine, Tokyo, Japan

    Zhi-Qing Hu & Wei-Hua Zhao

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  1. Zhi-Qing Hu
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Correspondence to Zhi-Qing Hu.

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Hu, ZQ., Zhao, WH. Critical role of PD-1/PD-L1 pathway in generation and function of follicular regulatory T cells. Cell Mol Immunol 10, 286–288 (2013). https://doi.org/10.1038/cmi.2013.15

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