Differential expression of PD-L1 and PD-L2, ligands for an inhibitory receptor PD-1, in the cells of lymphohematopoietic tissues

Ishida, Masaharu; Iwai, Yoshiko; Tanaka, Yoshimasa; Okazaki, Taku; Freeman, Gordon J.; Minato, Nagahiro; Honjo, Tasuku

doi:10.1016/s0165-2478(02)00142-6

Cited by 257 publications

(206 citation statements)

References 17 publications

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“…A monoclonal antibody (clone 243) for AID was prepared as described (35) except for the preparation of antigen. In brief, murine AID cDNA was cloned into expression vector pET16b (Novagen) to produce His-tagged recombinant AID protein in bacterial strain BL21(DE3).…”

Section: Rt-pcrmentioning

confidence: 99%

Negative regulation of activation-induced cytidine deaminase in B cells

Muto¹,

Okazaki²,

Yamada

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Activation-induced cytidine deaminase (AID) is required for both CSR and SHM because AID deficiency in mouse and human completely abolishes these two genetic alterations (2, 3). In addition to AID, CSR and SHM require transcription of target DNAs, S regions, and V regions, respectively (4-10). AID expression in non-B cells such as fibroblasts and T cells can induce CSR and SHM on transfected artificial constructs if the target DNA is actively transcribed (11-13). Therefore, AID and target transcription appear to be essential and sufficient for CSR and SHM in non-B as well as B cells. However, studies on transgenic (Tg) mouse lines ubiquitously expressing AID showed neither distortion of the B220 ϩ B cell population nor increase in serum IgG levels (14). Although all mice died by 80 weeks because of T cell lymphomas, no B cell lymphomas were observed in the Tg mice (14). These observations have raised a possibility that Tg AID is negatively regulated in B cells. However, we could not exclude the possibility that dysregulation of T cells by a very early onset of T lymphomas may perturb B cell responses in AID-Tg mice.It is therefore important to test the effects of constitutive AID expression in B cells using a more defined system. We thus generated Tg mice, which express AID constitutively only in B cells, and crossed them with AID-deficient mice. Using this system, we found that the Tg AID, despite its abundance, is much less efficient for CSR and SHM than the endogenous AID, suggesting that AID is negatively regulated in B cells.

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Section: Rt-pcrmentioning

confidence: 99%

Negative regulation of activation-induced cytidine deaminase in B cells

Muto¹,

Okazaki²,

Yamada

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…Two B7 family molecules have been identified as the ligands for PD-1: B7-H1/PD-L1 [16,17] (hereafter referred to as B7-H1) and B7-DC/PD-L2 [18,19] (hereafter referred to as B7-DC). B7-H1 is broadly expressed on most lymphohematopoietic cells, normal tissue cells stimulated by cytokines, and a variety of tumor cells; B7- DC expression is highly restricted to DC and activated macrophages [16,[20][21][22]. The differential expression of B7-H1 and B7-DC suggests differential contributions of these two ligands to PD-1-mediated immune regulation in vivo.…”

Section: Introductionmentioning

confidence: 99%

Preferential contribution of B7‐H1 to programmed death‐1‐mediated regulation of hapten‐specific allergic inflammatory responses

et al. 2003

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Programmed death-1 (PD-1) and its ligands, B7-H1/PD-L1 and B7-DC/PD-L2, are new CD28-B7 family members that may be involved in the regulation of immune responses. We examined the roles of these molecules in mouse hapten-induced contact hypersensitivity (CH). Administration of anti-PD-1 mAb at sensitization significantly enhanced and prolonged ear swelling. Treatment with anti-B7-H1 mAb, but not anti-B7-DC mAb, also enhanced CH reactions. The anti-PD-1 mAb treatment at sensitization significantly increased the T cell number of draining lymph nodes (DLN). B7-H1 was induced on activated T cells and antigen-presenting cells (APC) in the skin and the DLN, whereas B7-DC expression was restricted to dendritic cells (DC) in the dermis and the DLN. A particular subset of DC, B7-H1 + B7-DC -CD86 low , was found in sensitized DLN. The blockade of B7-H1, but not B7-DC, dramatically enhanced the initial T cell proliferative responses against hapten-pulsed DLN APC, suggesting the preferential contribution of B7-H1 to the T cell-APC interaction. Our results demonstrate the regulatory role of PD-1 and the differential roles of B7-H1 and B7-DC in hapten-induced immune responses. The PD-1-B7-H1 pathway may play a unique role in regulating inflammatory responses.

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“…Importantly, targeting PD-1/PD-L1 interactions can also improve the efficacy of adoptive cell therapies in tumors or chronic viral infections. [11][12][13][14] In some instances PD-1 blockade has been shown to mediate tumor eradication, [15][16][17] resulting in impressive and highly encouraging clinical results. Indeed, accumulating data indicate that the administration of an mAb to PD-1, used alone or in combination with other drugs, might provide a highly successful therapeutic tool in different types of advanced tumors, including melanoma, lung cancer, and ovarian carcinoma.…”

mentioning

confidence: 99%

Identification of a subset of human natural killer cells expressing high levels of programmed death 1: A phenotypic and functional characterization

Pesce

Greppi

Tabellini

et al. 2017

Journal of Allergy and Clinical Immunology

389

386

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Background: Programmed death 1 (PD-1) is an immunologic checkpoint that limits immune responses by delivering potent inhibitory signals to T cells on interaction with specific ligands expressed on tumor/virus-infected cells, thus contributing to immune escape mechanisms. Therapeutic PD-1 blockade has been shown to mediate tumor eradication with impressive clinical results. Little is known about the expression/function of PD-1 on human natural killer (NK) cells. Objective: We sought to clarify whether human NK cells can express PD-1 and analyze their phenotypic/functional features. Methods: We performed multiparametric cytofluorimetric analysis of PD-1 1 NK cells and their functional characterization using degranulation, cytokine production, and proliferation assays. Results: We provide unequivocal evidence that PD-1 is highly expressed (PD-1 bright ) on an NK cell subset detectable in the peripheral blood of approximately one fourth of healthy subjects. These donors are always serologically positive for human cytomegalovirus. PD-1 is expressed by CD56 dim but not CD56 bright NK cells and is confined to fully mature NK cells characterized by the NKG2A 2 KIR 1 CD57 1 phenotype. Proportions of PD-1 bright NK cells were higher in the ascites of a cohort of patients with ovarian carcinoma, suggesting their

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Differential expression of PD-L1 and PD-L2, ligands for an inhibitory receptor PD-1, in the cells of lymphohematopoietic tissues

Cited by 257 publications

References 17 publications

Negative regulation of activation-induced cytidine deaminase in B cells

Negative regulation of activation-induced cytidine deaminase in B cells

Preferential contribution of B7‐H1 to programmed death‐1‐mediated regulation of hapten‐specific allergic inflammatory responses

Identification of a subset of human natural killer cells expressing high levels of programmed death 1: A phenotypic and functional characterization

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