Interleukin-27 Priming of T Cells Controls IL-17 Production In trans via Induction of the Ligand PD-L1

Hirahara, Kiyoshi; Ghoreschi, Kamran; Xiang, Yang; Takahashi, Hayato; Laurence, Arian; Vahedi, Golnaz; Sciumé, Giuseppe; Hall, Aisling O’Hara; Dupont, Christian; Francisco, Loise; Chen, Qian; Tanaka, Masao; Kanno, Yuka; Sun, Hongwei; Sharpe, Arlene H.; Hunter, Christopher A.; O’Shea, John J.

doi:10.1016/j.immuni.2012.03.024

Cited by 216 publications

(221 citation statements)

References 51 publications

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“…However, when evaluating classical maturation markers of APCs, such as expression of costimulatory molecules, we did not observe any difference in expression levels, at least in vitro. Another publication described in trans control of T H 17 differentiation via B7-H1 expression on adjacent CD4 + T cells (27). In contrast to these findings, we did not observe a particular increase in T H 17 responses due to lack of B7-H1 on T cells, either in vitro or in vivo.…”

Section: Discussioncontrasting

confidence: 99%

B7-H1 shapes T-cell–mediated brain endothelial cell dysfunction and regional encephalitogenicity in spontaneous CNS autoimmunity

Klotz

Kuzmanov

Hucke

et al. 2016

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

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Molecular mechanisms that determine lesion localization or phenotype variation in multiple sclerosis are mostly unidentified. Although transmigration of activated encephalitogenic T cells across the bloodbrain barrier (BBB) is a crucial step in the disease pathogenesis of CNS autoimmunity, the consequences on brain endothelial barrier integrity upon interaction with such T cells and subsequent lesion formation and distribution are largely unknown. We made use of a transgenic spontaneous mouse model of CNS autoimmunity characterized by inflammatory demyelinating lesions confined to optic nerves and spinal cord (OSE mice). Genetic ablation of a single immune-regulatory molecule in this model [i.e., B7-homolog 1 (B7-H1, PD-L1)] not only significantly increased incidence of spontaneous CNS autoimmunity and aggravated disease course, especially in the later stages of disease, but also importantly resulted in encephalitogenic T-cell infiltration and lesion formation in normally unaffected brain regions, such as the cerebrum and cerebellum. Interestingly, B7-H1 ablation on myelin oligodendrocyte glycoprotein-specific CD4 + T cells, but not on antigen-presenting cells, amplified T-cell effector functions, such as IFN-γ and granzyme B production. Therefore, these T cells were rendered more capable of eliciting cell contact-dependent brain endothelial cell dysfunction and increased barrier permeability in an in vitro model of the BBB. Our findings suggest that a single immuneregulatory molecule on T cells can be ultimately responsible for localized BBB breakdown, and thus substantial changes in lesion topography in the context of CNS autoimmunity.neuroinflammation | multiple sclerosis | spontaneous EAE | CNS lesion distribution | blood-brain barrier M ultiple sclerosis (MS) is the most common chronic inflammatory demyelinating disease of the CNS. Disease pathogenesis is initiated by peripheral activation of autoimmune T lymphocytes by yet unknown mechanisms, followed by T-cell expansion and subsequent migration across the complex structure of the blood-brain barrier (BBB). Within the CNS, entry of this first wave of T cells elicits recruitment of other immune cells, which together evoke a local inflammatory process ultimately resulting in demyelination, as well as axonal and neuronal damage (1). Several histological MS subtypes have been described with regard to lesion distribution and cellular composition (2). The reasons underlying distinct lesion development at different anatomical sites still remain however largely elusive: Some authors have proposed that the nature and expression pattern of the target autoantigen might play a role (3, 4). Others have observed an influence of the HLA complex and its role in shaping antigen presentation, thus suggesting that T-cell antigen specificity might impact the location of inflammation (5). Additionally, T-cell polarization into distinct T helper subtypes, as well as their expression pattern of chemokine receptors and adhesion molecules, has been implicated in determining the lo...

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Section: Discussioncontrasting

confidence: 99%

B7-H1 shapes T-cell–mediated brain endothelial cell dysfunction and regional encephalitogenicity in spontaneous CNS autoimmunity

Klotz

Kuzmanov

Hucke

et al. 2016

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

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“…(16)(17)(18)(19) showed that NSCLC over-expressed PD-L1 has ranged from 19% to 100%. However, in this study, the percentage of PDL1-positive cases in NSCLC was 56% and the expression increased with the more advanced stage.…”

Section: Resultsmentioning

confidence: 99%

Prognostic significance of programmed cell death ligand 1 (pd-l1), cd8+ tumor-infiltrating lymphocytes and p53 in non-small cell lung cancer: an immunohistochemical study

Rashed

Abdelrahman²,

Abdelgawad³

et al. 2017

TJPATH

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IntRoduCtIonLung cancer ranks the first in the incidence and mortality rates amongst all malignancies worldwide. Non-small cell lung cancer (NSCLC) constitutes 80% -85% of all diagnosed cases and more than 70% of NSCLC are diagnosed as an advanced or late disease (1).Recognition of tumor antigens by t cells leads to activation of anti-tumor immune reaction mainly by cytotoxic CD+8 tumor infiltrating lymphocytes (tiLs), but malignant cells may have many pathways to evade the immunological destruction. PD-1 is a co-stimulatory molecule on t-cells that inhibits t cell activation. PD-1, which is a 288-amino acid cell-surface protein, can bind two ligands, PD-L1 and PD-L2, which negatively control the immune response. tumor cells express PD-L1 can inhibit t cell-mediated immune response and can progress to distant metastasis (2,3). CD8 marker is expressed on cytotoxic t cells, natural killer, and dendritic cells. CD8+ t cells are a major component of the cell-mediated immune system against malignant cells. CD8+ t cells undergo differentiation to effector cytotoxic t cells. Then the effector CD8+ cells undergo apoptosis leaving memory cells when a pathogenic response is resolved. Memory t cells and cytotoxic t cells are associated with a more favorable prognosis in NSCLC (4).PD-L1 over-expression has been proved to be a poor prognostic marker in many human cancers (5). PD-1/ PD-L1 interaction suppresses CD8+ tiLs survival and proliferation and leads to apoptosis of tumor-infiltrating lymphocytes. PD-L1 over-expression in tumor cells in a syngeneic transplant model of tumor cells makes them evade from cytotoxic tiLs (6). AbStRACtObjective: Programmed cell death ligand-1 interacts with the immune receptors on the surface of CD8+ tumor infiltrating lymphocytes and PD-1, thereby blocking its anti-tumor activity. therapeutics suppression of this interaction will show a promise in the treatment of non-small cell lung cancer by restoring the functional anti-tumor t-cell activity. We aimed to evaluate the association between the immunohistochemical expression of PD-L1, stromal CD8+ tumor infiltrating lymphocytes and p53 with the clinicopathological characteristics, response to chemotherapy, progression-free-survival, and overall survival. Material and Method:We examined the immunohistochemical expression of PD-L1, stromal CD8+ tiLs, and p53 expression in 50 patients with advanced stage (iii&iV) non-small cell lung cancer.Results: PD-L1 was expressed in 56% of the studied cases. PD-L1 expression was related to unfavorable response to the therapy without significant difference. PD-L1 expression was significantly associated with disease progression, poor progression-free-survival & overall survival. CD8+ tiLs were high in 32% of the cases. tumors with high CD8+ tiLs showed a partial response to therapy and had a better progression-free-survival and overall survival. p53 expressed in 82% of the studied cases. there was a significant negative association between PD-L1 and CD8+ tiLs (p=0.009), while a non-significant association wa...

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“…In this model, mice that received bystander CD4 + T cell alone without transgenic T cells did not develop disease (54). Thus, 2D2 T cells are the unique inducers of EAE after MOG immunization in this setting, and EAE can be prevented by cotransfer of bystander CD4 + T cell populations (54). Clinical signs of disease were monitored, and mice were killed 19 d after immunization.…”

Section: Eomes Deficiency Enhances the Capacity Of Cd4 + T Cells To Pmentioning

confidence: 89%

“…Experimental autoimmune encephalitis (EAE) is a widely used model for multiple sclerosis, and Foxp3 + Treg play a significant role in the inhibition of pathology in EAE (53). To test the regulatory capacity of Eomes-deficient T cells, we adoptively transferred CD4 + T cells from Eomes KO or control mice together with 2D2 TCR-transgenic T cells that recognized MOG peptide, as previously described (54). After transfer, mice were immunized with MOG, CFA, and pertussis toxin as per standard protocol.…”

Section: Eomes Deficiency Enhances the Capacity Of Cd4 + T Cells To Pmentioning

confidence: 99%

Eomesodermin Expression in CD4+ T Cells Restricts Peripheral Foxp3 Induction

Lupar¹,

Brack

Garnier

et al. 2015

The Journal of Immunology

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CD4+ T cells polarize into effector Th subsets characterized by signature transcription factors and cytokines. Although T-bet drives Th1 responses and represses the alternative Th2, Th17, and Foxp3+ regulatory T cell fates, the role of the T-bet–related transcription factor eomesodermin (Eomes) in CD4+ T cells is less well understood. In this study, we analyze the expression and effects of Eomes in mouse CD4+ T lymphocytes. We find that Eomes is readily expressed in activated CD4+ Th1 T cells in vivo. Eomes+ CD4+ T cells accumulated in old mice, under lymphopenic conditions in a T cell transfer model of colitis, and upon oral Ag administration. However, despite its expression, genetic deletion of Eomes in CD4+ T cells did not impact on IFN-γ production nor increase Th2 or Th17 responses. In contrast, Eomes deficiency favored the accumulation of Foxp3+ cells in old mice, after in vivo differentiation of Eomes-deficient naive CD4+ T cells, and in response to oral Ag in a cell-intrinsic way. Enforced Eomes expression during in vitro regulatory T cell induction also reduced Foxp3 transcription. Likewise, bystander Eomes-deficient CD4+ T cells were more efficient at protecting from experimental autoimmune encephalitis compared with wild-type CD4+ T cells. This enhanced capacity of Eomes-deficient CD4+ T cells to inhibit EAE in trans was associated with an enhanced frequency of Foxp3+ cells. Our data identify a novel role for Eomes in CD4+ T cells and indicate that Eomes expression may act by limiting Foxp3 induction, which may contribute to the association of EOMES to susceptibility to multiple sclerosis.

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Interleukin-27 Priming of T Cells Controls IL-17 Production In trans via Induction of the Ligand PD-L1

Cited by 216 publications

References 51 publications

B7-H1 shapes T-cell–mediated brain endothelial cell dysfunction and regional encephalitogenicity in spontaneous CNS autoimmunity

B7-H1 shapes T-cell–mediated brain endothelial cell dysfunction and regional encephalitogenicity in spontaneous CNS autoimmunity

Prognostic significance of programmed cell death ligand 1 (pd-l1), cd8+ tumor-infiltrating lymphocytes and p53 in non-small cell lung cancer: an immunohistochemical study

Eomesodermin Expression in CD4+ T Cells Restricts Peripheral Foxp3 Induction

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