Peripheral deletional tolerance of alloreactive CD8 but not CD4 T cells is dependent on the PD-1/PD-L1 pathway

Haspot, Fabienne; Fehr, Thomas; Gibbons, Carrie; Zhao, Genshi; Hogan, Timothy; Honjo, Tasuku; Freeman, Gordon J.; Sykes, Megan

doi:10.1182/blood-2007-12-127449

Cited by 62 publications

(64 citation statements)

References 32 publications

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“…These animals were then used as recipients of 3 Gy TBI/anti-CD154 with allogeneic BMT and killed on day 7 for ex vivo analysis of PD-1 expression. As observed previously, 13 polyclonal WT CD8 T cells in control WT/WT synchimeric recipients up-regulated PD-1 compared with conditioned control animals (dotted line) that did not receive BM ( Figure 6B). Surprisingly, in WT/NFAT1 KO synchimeric recipients of allogeneic BMT, up-regulation of PD-1 was significantly more pronounced on the polyclonal NFAT1 KO CD8 T cells relative to the WT CD8 T cells in the same animal ( Figure 6C-D) regardless of whether anti-CD154 was administered.…”

Section: Pd-1 Expression On Cd8 T Cells Is Independent Of Nfat1supporting

confidence: 84%

“…12,13 In brief, 5 million BM cells from 2C-TCR tg B6 mice were transplanted into naive B6 mice treated with 3 Gy TBI on the same day. After 8 weeks, the percentage of 2C CD8 cells identified by the 1B2 clonotypic mAb ranged from 12.4% to 47.0%.…”

Section: C/b6 Syn-chimerasmentioning

confidence: 99%

“…12 To investigate whether CsA treatment interfered with deletion of peripheral donor-reactive CD8 cells, we used the 2C TCR transgenic model in which CD8 T cells express a directly alloreactive TCR recognizing L d . In a first step, we generated 2C/B6 syn-chimeric mice (described in Haspot et al 13 ) expressing the 2C TCR on a subpopulation of CD8 T cells. These mice then received 3 Gy TBI/anti-CD154 followed by allogeneic BMT from a donor strain expressing the L d ligand (B10.A), with or without CsA treatment for 28 days.…”

Section: Csa Interferes With Cd8 Tolerance Induced By Allo-bmt With Amentioning

confidence: 99%

“…13 To test this hypothesis, animals containing both WT and NFAT1 Ϫ/Ϫ hematopoietic cells were generated as depicted in Figure 6A. These animals were then used as recipients of 3 Gy TBI/anti-CD154 with allogeneic BMT and killed on day 7 for ex vivo analysis of PD-1 expression.…”

Section: Pd-1 Expression On Cd8 T Cells Is Independent Of Nfat1mentioning

confidence: 99%

“…12 In this process PD-1 engagement is essential for CD8 but not CD4 tolerance. 13 The authors of studies in large animals and rodents 14,15 have suggested that calcineurin inhibition blocks the graft-prolonging effects of anti-CD154. In other studies in monkeys and humans, 10,16 investigators have successfully used calcineurin inhibitors in protocols achieving tolerance with combined kidney and BMT.…”

Section: Introductionmentioning

confidence: 99%

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A CD8 T cell–intrinsic role for the calcineurin-NFAT pathway for tolerance induction in vivo

Fehr

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et al. 2010

Blood

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Section: Pd-1 Expression On Cd8 T Cells Is Independent Of Nfat1supporting

confidence: 84%

Section: C/b6 Syn-chimerasmentioning

confidence: 99%

Section: Csa Interferes With Cd8 Tolerance Induced By Allo-bmt With Amentioning

confidence: 99%

Section: Pd-1 Expression On Cd8 T Cells Is Independent Of Nfat1mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A CD8 T cell–intrinsic role for the calcineurin-NFAT pathway for tolerance induction in vivo

Fehr

Lucas

Kurtz

et al. 2010

Blood

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Ex vivo anchored PD‐L1 functionally prevent in vivo renal allograft rejection

Luo

Liao

Zhang

et al. 2022

Bioengineering & Transla Med

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Organ transplantation is the optimal treatment for patients with end-stage diseases.T cell activation is a major contributing factor toward the trigger of rejection. Induction therapy with T cell depleting agent is a common option but increases the risk of severe systemic infections. The ideal therapy should precisely target the allograft.Here, we developed a membrane-anchored-protein PD-L1 (map-PD-L1), which effectively anchored onto the surface of rat glomerular endothelial cells (rgEC). The expression of PD-L1 increased directly with map-PD-L1 concentration and incubation time. Moreover, map-PD-L1 was even stably anchored to rgEC at low temperature. Map-PD-L1 could bind to PD-1 and significantly promote T cell apoptosis and inhibited T cell activation. Using kidney transplantation models, we found that ex vivo perfusion of donor kidneys with map-PD-L1 significantly protected grafts against acute injury without using any immunosuppressant. We found map-PD-L1 could reduce T cell graft infiltration and increase intragraft Treg infiltration, suggesting a long-term effect in allograft protection. More importantly, modifying donor organs in vitro was not only safe, but also significantly reduced the side effects of systemic application. Our results suggested that ex vivo perfusion of donor organ with map-PD-L1 might provide a viable clinical option for organ-targeted induction therapy in organ transplantation.

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High expression of PD-L1 in lung cancer may contribute to poor prognosis and tumor cells immune escape through suppressing tumor infiltrating dendritic cells maturation

et al. 2010

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The immunohistochemical analysis was used to evaluate the expression of PD-L1 in 109 non-small cell lung cancer (NSCLC) tissues and para-tumor tissues. Associations between expressed PD-L1 and tumor histological types, degree of differentiation, and lymph node metastasis were calculated, and overall survival was assessed. Meanwhile, immunohistochemistry and immunofluorescence double labeling technique were performed to detect the expressions of PD-L1, CD1α, and CD83 on TIDC of 20 lung cancer tissues, and the expression of PD-L1 in CD1α+DCs and CD83+DCs and their significances were also explored. We found that the expression rate of PD-L1 in NSCLC was associated with histological types and overall survival. Patients with either adenocarcinoma or survival time after surgery less than 3 years showed higher expression rate of PD-L1. Furthermore, Cox model analysis indicated that PD-L1 might be regarded as a poor prognostic factor. PD-L1 could be also detected in CD1α+ immature DC in NSCLC, indicating that as a class of key anti-tumor immunocyte in tumor microenvironment, DC expressing PD-L1 itself might play an important role in keeping its immature status and contributing to tumor cells immune escape and disease progression.

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Peripheral deletional tolerance of alloreactive CD8 but not CD4 T cells is dependent on the PD-1/PD-L1 pathway

Cited by 62 publications

References 32 publications

A CD8 T cell–intrinsic role for the calcineurin-NFAT pathway for tolerance induction in vivo

A CD8 T cell–intrinsic role for the calcineurin-NFAT pathway for tolerance induction in vivo

Ex vivo anchored PD‐L1 functionally prevent in vivo renal allograft rejection

High expression of PD-L1 in lung cancer may contribute to poor prognosis and tumor cells immune escape through suppressing tumor infiltrating dendritic cells maturation

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