The receptor PD-1 controls follicular regulatory T cells in the lymph nodes and blood
Peter T. Sage,Loise M. Francisco,Loise M. Francisco,Christopher V. Carman,Arlene H. Sharpe,Arlene H. Sharpe +5 more
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TLDR
These findings demonstrate mechanisms by which the PD-1 pathway regulates antibody production and help reconcile inconsistencies surrounding the role of this pathway in humoral immunity.Abstract:
CD4(+)CXCR5(+)Foxp3(+) follicular regulatory T cells (T(FR) cells) inhibit humoral immunity mediated by CD4(+)CXCR5(+)Foxp3(-) follicular helper T cells (T(FH) cells). Although the inhibitory receptor PD-1 is expressed by both cell types, its role in the differentiation of T(FR) cells is unknown. Here we found that mice deficient in PD-1 and its ligand PD-L1 had a greater abundance of T(FR) cells in the lymph nodes and that those T(FR) cells had enhanced suppressive ability. We also found substantial populations of T(FR) cells in mouse blood and demonstrated that T(FR) cells in the blood homed to lymph nodes and potently inhibited T(FH) cells in vivo. T(FR) cells in the blood required signaling via the costimulatory receptors CD28 and ICOS but were inhibited by PD-1 and PD-L1. Our findings demonstrate mechanisms by which the PD-1 pathway regulates antibody production and help reconcile inconsistencies surrounding the role of this pathway in humoral immunity.read more
Citations
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T follicular helper cell differentiation, function, and roles in disease
TL;DR: There has been dramatic advances in this young field, but there is much to be learned about Tfh cell biology in the interest of applying that knowledge to biomedical needs.
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The diverse functions of the PD1 inhibitory pathway.
TL;DR: The diverse roles of the PD1 pathway in regulating immune responses are discussed and how this knowledge can improve cancer immunotherapy as well as restore and/or maintain tolerance during autoimmunity and transplantation.
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Follicular Helper T Cells
TL;DR: The realization that follicular T cells are heterogeneous, comprising helper and regulatory subsets, has raised questions regarding a possible division of labor in germinal center B cell selection and elimination.
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Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations.
TL;DR: The mechanisms of action and the limitations of anti-PD-1/PD-L1 and anti-CTLA-4 antibodies which are the two types of checkpoint inhibitors currently available to patients are examined and the future avenues of their use in melanoma and other cancers are explored.
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A rheostat for immune responses: the unique properties of PD-1 and their advantages for clinical application.
TL;DR: The molecular mechanisms of the functions of PD-1, in conjunction with the mild, chronic and strain-specific autoimmune phenotypes ofPD-1-deficient mice, suggest that immunoregulation by PD- 1 is rather antigen specific and is mainly cell intrinsic.
References
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