The DOI matches its Crossref record; 76 of the 76 references it cites were found in a registry or an index.
PD-L1 regulates the development, maintenance, and function of induced regulatory T cells
Open accessAbstract
Both the programmed death (PD) 1–PD-ligand (PD-L) pathway and regulatory T (T reg) cells are instrumental to the maintenance of peripheral tolerance. We demonstrate that PD-L1 has a pivotal role in regulating induced T reg (iT reg) cell development and sustaining iT reg cell function. PD-L1−/− antigen-presenting cells minimally convert naive CD4 T cells to iT reg cells, showing the essential role of PD-L1 for iT reg cell induction. PD-L1–coated beads induce iT reg cells in vitro, indicating that PD-L1 itself regulates iT reg cell development. Furthermore, PD-L1 enhances and sustains Foxp3 expression and the suppressive function of iT reg cells. The obligatory role for PD-L1 in controlling iT reg cell development and function in vivo is illustrated by a marked reduction in iT reg cell conversion and rapid onset of a fatal inflammatory phenotype in PD-L1−/−PD-L2−/− Rag−/− recipients of naive CD4 T cells. PD-L1 iT reg cell development is mediated through the down-regulation of phospho-Akt, mTOR, S6, and ERK2 and concomitant with the up-regulation of PTEN, all key signaling molecules which are critical for iT reg cell development. Thus, PD-L1 can inhibit T cell responses by promoting both the induction and maintenance of iT reg cells. These studies define a novel mechanism for iT reg cell development and function, as well as a new strategy for controlling T reg cell plasticity.
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Cites
Control of Regulatory T Cell Development by the Transcription Factor Foxp3
Hori, S., Nomura, T., & Sakaguchi, S. (2003) · Science · doi:10.1126/science.1079490 · Cited by 8,187
Foxp3 programs the development and function of CD4+CD25+ regulatory T cells
Fontenot, J. D., Gavin, M. A., & Rudensky, A. Y. (2003) · Nature Immunology · doi:10.1038/ni904 · Cited by 7,745
Bettelli, E., Carrier, Y., Gao, W., Korn, T., Strom, T. B., Oukka, M., Weiner, H. L., & Kuchroo, V. K. (2006) · Nature · doi:10.1038/nature04753 · Cited by 6,992
Self-citationPD-1 and Its Ligands in Tolerance and Immunity
Keir, M. E., Butte, M. J., Freeman, G. J., & Sharpe, A. H. (2008) · Annual Review of Immunology · doi:10.1146/annurev.immunol.26.021607.090331 · Cited by 5,378
Self-citationRegulatory T Cells and Immune Tolerance
Sakaguchi, S., Yamaguchi, T., Nomura, T., & Ono, M. (2008) · Cell · doi:10.1016/j.cell.2008.05.009 · Cited by 5,325
Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion
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Restoring function in exhausted CD8 T cells during chronic viral infection
Barber, D. L., Wherry, E. J., Masopust, D., Zhu, B., Allison, J. P., Sharpe, A. H., Freeman, G. J., & Ahmed, R. (2006) · Nature · doi:10.1038/nature04444 · Cited by 3,986
Self-citationVignali, D. A. A., Collison, L. W., & Workman, C. J. (2008) · Nature Reviews Immunology · doi:10.1038/nri2343 · Cited by 3,463
Iwai, Y., Ishida, M., Tanaka, Y., Okazaki, T., Honjo, T., & Minato, N. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.192461099 · Cited by 3,203
Cited by
The blockade of immune checkpoints in cancer immunotherapy
Pardoll, D. M. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3239 · Cited by 13,838
A guide to cancer immunotherapy: from T cell basic science to clinical practice
Waldman, A. D., Fritz, J. M., & Lenardo, M. J. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-020-0306-5 · Cited by 4,154
Molecular mechanisms of T cell co-stimulation and co-inhibition
Chen, L., & Flies, D. B. (2013) · Nature Reviews Immunology · doi:10.1038/nri3405 · Cited by 3,114
CTLA-4 and PD-1 Pathways: Similarities, Differences, and Implications of Their Inhibition
Buchbinder, E. I., & Desai, A. (2016) · American Journal of Clinical Oncology · doi:10.1097/coc.0000000000000239 · Cited by 2,360
“PD-L1 has been shown to contribute to the conversion of naive CD4 + T cells to Treg cells34 and to inhibit T-cell responses by promoting the induction and maintenance of Tregs.35 Consistent with these findings, PD-1 blockade can reverse Tregmediated suppression of effector T cells in vitro.36 PD-1 binding with its lig…”
ResultThe PD‐1 pathway in tolerance and autoimmunity
Francisco, L. M., Sage, P. T., & Sharpe, A. H. (2010) · Immunological Reviews · doi:10.1111/j.1600-065x.2010.00923.x · Cited by 2,300
Self-citation
Metadata
- Authors
- Francisco, L. M., Salinas, V. H., Brown, K. E., Vanguri, V. K., Freeman, G. J., Kuchroo, V. K., & Sharpe, A. H.
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2009-12-14
- Volume
- 206
- Issue
- 13
- Pages
- 3015-3029
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2108933323
- Cited by
- 2,079
- References
- 76
- FWCI
- 23.93
- Type
- journal article
- Language
- en
- Open access
- hybrid
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