Frontline: Neuropilin‐1: a surface marker of regulatory T cells

Bruder, Dunja; Probst‐Kepper, Michael; Westendorf, Astrid M.; Geffers, Robert; Beissert, Stefan; Loser, Karin; Boehmer, Harald von; Buer, Jan; Hansen, Wiebke

doi:10.1002/eji.200324799

Cited by 404 publications

(352 citation statements)

References 21 publications

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“…1A and C). These results confirm and extend the finding of Bruder et al [3] and demonstrate that the Nrp-1-specific expression on Treg is not limited to a specific organ but is rather a general characteristic of these cells in mice.…”

Section: Resultssupporting

confidence: 92%

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Neuropilin‐1 is not a marker of human Foxp3⁺ Treg

et al. 2009

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Treg are immune cells that play a critical role in the regulation of the immune response. Although the transcription factor Foxp3 is widely accepted as the standard marker of Treg, specific surface markers are needed to better characterize these cells and decipher their mechanisms of action. Neuropilin-1 (Nrp-1), a membrane protein primarily involved in the nervous system, was identified as a specific marker of murine Treg, but its expression has not been rigorously investigated in human Treg. Here we show that in contrast to murine Treg and regardless of their origins (blood, thymus, spleen, lymph node or tonsil), human Foxp3 1 Treg do not specifically express Nrp-1. However, a population of Foxp3 À Nrp-1 1 T cells can be detected in human secondary lymphoid organs, and Nrp-1 expression is induced on peripheral blood T lymphocytes upon in vitro activation. We conclude that Nrp-1 cannot be used as a specific marker of human Treg, but might represent a novel activation marker of human T cells both in vitro and in vivo.

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Section: Resultssupporting

confidence: 92%

“…In order to identify specific cell surface markers of Treg, Bruder et al have shown by using a transcriptomic approach that in contrast to Tconv, neuropilin-1 (Nrp-1) is strongly and constitutively expressed in murine Treg [3].…”

Section: Introductionmentioning

confidence: 99%

Neuropilin‐1 is not a marker of human Foxp3⁺ Treg

et al. 2009

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“…2A, B). Neuropilin-1 is claimed to be a novel and very sensitive marker for Treg [34]. Our data strongly suggest an expansion of the Treg population in animals treated with CD4 + CD25 + cells.…”

Section: Resultssupporting

confidence: 58%

“…In fact, CD25 is used in the Immunomodulation decidua as an activation marker rather than a marker for Treg [28,33]. For having a more confidential marker of Treg activity, we analyzed the foxp3 and neuropilin-1 [34] mRNA levels in whole tissue by real-time RT-PCR (decidua and placenta, respectively). We observed a diminution in the foxp3 and neuropilin-1 levels at the fetal-maternal interface in abortion prone-mice.…”

Section: Resultsmentioning

confidence: 99%

Regulatory T cells induce a privileged tolerant microenvironment at the fetal‐maternal interface

et al. 2005

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The mechanisms underlying immune tolerance during pregnancy are poorly understood. In this regard, Treg seem to play an important role in mediating maternal tolerance to the fetus. We proposed a crucial role of T regulatory cells (Treg) in avoiding immunological rejection of the fetus after observing diminished number and function of Treg in abortion-prone mice. We further confirmed the protective role of Treg during pregnancy by transferring pregnancy-induced Treg into abortion-prone mice, which prevented rejection. Here, we analyzed the mechanisms involved in Treg-mediated protection. As expected, Treg therapy prevented abortion, while expanding the peripheral and thymic Treg population. Surprisingly, the decidual levels of the Th1 cytokines IFN-c and TNF-a were not diminished after therapy. Interestingly, the mRNA levels of leukemia inhibitory factor, TGF-b and heme oxygenase-1 at the fetal-maternal interface were dramatically up-regulated after Treg transfer, while the levels of indolamine 2,3-dioxygenase remained unchanged. Our data suggest that Treg treatment can not prevent T cell infiltration or high Th1 levels but is able to create a privileged tolerant microenvironment at the fetal-maternal interface, further shedding light onto the molecular mechanisms involved in pregnancy tolerance.

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“…In patients with SCCHN, we have recently described a significant enrichment in CD4 þ CD25 þ T cells in the peripheral blood and particularly among tumour-infiltrating lymphocytes (Albers et al, 2004). However, it now appears that T reg are a heterogenous population within CD4 þ T cells, and that a subset of CD4 þ CD25 þ T cells could be subdivided into different functional subsets based on expression of novel markers such as GITR, Foxp3 or neurophilin-1 (Cosmi et al, 2003;Ramsdell, 2003;Bruder et al, 2004;Ronchetti et al, 2004). Further, a subset of these cells could represent activated CD4 cells expressing the CD25 þ receptor.…”

Section: Discussionmentioning

confidence: 99%

Characteristics of CD4+CD25+ regulatory T cells in the peripheral circulation of patients with head and neck cancer

et al. 2005

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Patients with squamous cell carcinoma of the head and neck (SCCHN) have depressed antitumour immunity. The presence of CD4 þ CD25 þ (T reg ) cells in these patients might be, in part, responsible for downregulation of antitumour immune responses. To evaluate the frequency and characteristics of T reg in the peripheral circulation of patients with SCCHN, we used multicolour flow cytometry. Expression of CCR7, CD62L, z chain and Annexin V binding to T reg and non-T reg CD4 þ lymphocyte populations were evaluated. T reg were confirmed to be Foxp3 þ and GITR þ . The T reg frequency was significantly elevated in patients with active disease and those with no evidence of disease (NED) following curative therapies. Both T reg and non-T reg CD4 þ T cells in patients were significantly enriched in CCR7 À and CD62L À cell subsets. Although T reg in patients contained a higher proportion of double negative (CCR7 À CD62L À ) cells, the majority of T regs were CCR7 À CD62L þ . The proportion of Annexin V þ CD4 þ T cells was higher in patients (Po0.00005) than normal controls (NC), and T reg were significantly more sensitive to apoptosis than non-T reg in patients and NC. Expression of z was reduced in all subsets of CD4 þ T cells obtained from patients vs NC. The data suggest that T reg in patients with SCCHN largely contain T cells with the 'effector' phenotype, which bind Annexin V and have low z expression, consistent with their activation state and a rapid turnover in the peripheral circulation.

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Frontline: Neuropilin‐1: a surface marker of regulatory T cells

Cited by 404 publications

References 21 publications

Neuropilin‐1 is not a marker of human Foxp3⁺ Treg

Neuropilin‐1 is not a marker of human Foxp3⁺ Treg

Regulatory T cells induce a privileged tolerant microenvironment at the fetal‐maternal interface

Characteristics of CD4+CD25+ regulatory T cells in the peripheral circulation of patients with head and neck cancer

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Frontline: Neuropilin‐1: a surface marker of regulatory T cells

Cited by 404 publications

References 21 publications

Neuropilin‐1 is not a marker of human Foxp3+ Treg

Neuropilin‐1 is not a marker of human Foxp3+ Treg

Regulatory T cells induce a privileged tolerant microenvironment at the fetal‐maternal interface

Characteristics of CD4+CD25+ regulatory T cells in the peripheral circulation of patients with head and neck cancer

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Neuropilin‐1 is not a marker of human Foxp3⁺ Treg

Neuropilin‐1 is not a marker of human Foxp3⁺ Treg