ArticleInfection and immunity2016
Cooperation of PD-1 and LAG-3 Contributes to T-Cell Exhaustion in Anaplasma marginale-Infected Cattle.
Article in Infection and immunity, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
33 citing papers in PubMed, 49 citations in OpenAlex.
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- Study on the anti-tumor effect of PDL1-CAR-γδT cells constructed with nanobody sequences on glioblastoma.American journal of cancer research · 2025Article
- The role, relevance and management of immune exhaustion in bovine infectious diseases.Heliyon · 2024Review
- Temporal patterns of gene expression in response to inoculation with a virulent Anaplasma phagocytophilum strain in sheep.Scientific reports · 2023Article
- Development of a high-affinity anti-bovine PD-1 rabbit-bovine chimeric antibody using an efficient selection and large production system.Veterinary research · 2023Article
- LAG-3 Inhibitors: Novel Immune Checkpoint Inhibitors Changing the Landscape of Immunotherapy.Biomedicines · 2023Review
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- The PD-1/PD-L1 Pathway: A Perspective on Comparative Immuno-Oncology.Animals : an open access journal from MDPI · 2022Review
- Therapeutic targets and biomarkers of tumor immunotherapy: response versus non-response.Signal transduction and targeted therapy · 2022Review
- Enhancement of interleukin-2 production by bovine peripheral blood mononuclear cells treated with the combination of anti-programmed death-ligand 1 and cytotoxic T lymphocyte antigen 4 chimeric monoclonal antibodies.The Journal of veterinary medical science · 2022Article
- Programmed death-ligand 1 expression in swine chronic infections and enhancement of interleukin-2 production via programmed death-1/programmed death-ligand 1 blockade.Immunity, inflammation and disease · 2021Article
- Tick saliva-induced programmed death-1 and PD-ligand 1 and its related host immunosuppression.Scientific reports · 2021Article
- B7-H7 Is Inducible on T Cells to Regulate Their Immune Response and Serves as a Marker for Exhaustion.Frontiers in immunology · 2021Article
- Molecular and Clinical Characterization of LAG3 in Breast Cancer Through 2994 Samples.Frontiers in immunology · 2021Article
- Bovine Immunology: Implications for Dairy Cattle.Frontiers in immunology · 2021Review
- Betanodavirus and VER Disease: A 30-year Research Review.Pathogens (Basel, Switzerland) · 2020Review
- PD-L1 expression in equine malignant melanoma and functional effects of PD-L1 blockade.PloS one · 2020Article
- Upregulation of PD-L1 Expression by Prostaglandin EFrontiers in veterinary science · 2020Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
The CD4(+) T-cell response is central for the control of Anaplasma marginale infection in cattle. However, the infection induces a functional exhaustion of antigen-specific CD4(+) T cells in cattle immunized with A. marginale outer membrane proteins or purified outer membranes (OMs), which presumably facilitates the persistence of this rickettsia. In the present study, we hypothesize that T-cell exhaustion following infection is induced by the upregulation of immunoinhibitory receptors on T cells, such as programmed death 1 (PD-1) and lymphocyte activation gene 3 (LAG-3). OM-specific T-cell responses and the kinetics of PD-1-positive (PD-1(+)) LAG-3(+) exhausted T cells were monitored in A. marginale-challenged cattle previously immunized with OMs. Consistent with data from previous studies, OM-specific proliferation of peripheral blood mononuclear cells (PBMCs) and interferon gamma (IFN-γ) production were significantly suppressed in challenged animals by 5 weeks postinfection (wpi). In addition, bacteremia and anemia also peaked in these animals at 5 wpi. Flow cytometric analysis revealed that the percentage of PD-1(+) LAG-3(+) T cells in the CD4(+), CD8(+), and γδ T-cell populations gradually increased and also peaked at 5 wpi. A large increase in the percentage of LAG-3(+) γδ T cells was also observed. Importantly, in vitro, the combined blockade of the PD-1 and LAG-3 pathways partially restored OM-specific PBMC proliferation and IFN-γ production at 5 wpi. Taken together, these results indicate that coexpression of PD-1 and LAG-3 on T cells contributes to the rapid exhaustion of A. marginale-specific T cells following infection and that these immunoinhibitory receptors regulate T-cell responses during bovine anaplasmosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.