ArticleInfection and immunity2016
Bovine Immunoinhibitory Receptors Contribute to Suppression of Mycobacterium avium subsp. paratuberculosis-Specific T-Cell Responses.
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 28 papers.
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Who cites it
28 citing papers in PubMed, 42 citations in OpenAlex.
- Tick saliva reprograms macrophages into immunosuppressive hubs that regulate T-cell immunity in Rhipicephalus microplus infestation.Communications biology · 2026Article
- Paratuberculosis: a mucosal immunology perspective.Frontiers in immunology · 2026Review
- Evaluation of Immune Exhaustion and Co-Inhibitory Receptor Expression inPathogens (Basel, Switzerland) · 2024Article
- The role, relevance and management of immune exhaustion in bovine infectious diseases.Heliyon · 2024Review
- Development of a high-affinity anti-bovine PD-1 rabbit-bovine chimeric antibody using an efficient selection and large production system.Veterinary research · 2023Article
- Article
- Combined Immune Checkpoint Blockade Enhances Antiviral Immunity against Bovine Leukemia Virus.Journal of virology · 2023Article
- Prostaglandin EInfection and immunity · 2022Article
- 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
- Immune Evasion ofPathogens (Basel, Switzerland) · 2021Review
- The enhancement of Th1 immune response by anti-PD-L1 antibody in cattle infected with Mycobacterium avium subsp. paratuberculosis.The Journal of veterinary medical science · 2021Article
- Bovine Immunology: Implications for Dairy Cattle.Frontiers in immunology · 2021Review
- 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
- Article
- Cooperation of PD-1 and LAG-3 in the exhaustion of CD4Veterinary research · 2018Article
- T-cell Homing Therapy for Reducing Regulatory T Cells and Preserving Effector T-cell Function in Large Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Prostaglandin EInfection and immunity · 2018Article
- Mycoplasma bovis-Induced Inhibition of Bovine Peripheral Blood Mononuclear Cell Proliferation Is Ameliorated after Blocking the Immune-Inhibitory Programmed Death 1 Receptor.Infection and immunity · 2018Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Johne's disease (paratuberculosis) is a chronic enteritis in cattle that is caused by intracellular infection with Mycobacterium avium subsp. paratuberculosis. This infection is characterized by the functional exhaustion of T-cell responses to M. avium subsp. paratuberculosis antigens during late subclinical and clinical stages, presumably facilitating the persistence of this bacterium and the formation of clinical lesions. However, the mechanisms underlying T-cell exhaustion in Johne's disease are poorly understood. Thus, we performed expression and functional analyses of the immunoinhibitory molecules programmed death-1 (PD-1)/PD-ligand 1 (PD-L1) and lymphocyte activation gene 3 (LAG-3)/major histocompatibility complex class II (MHC-II) in M. avium subsp. paratuberculosis-infected cattle during the late subclinical stage. Flow cytometric analyses revealed the upregulation of PD-1 and LAG-3 in T cells in infected animals, which suffered progressive suppression of interferon gamma (IFN-γ) responses to the M. avium subsp. paratuberculosis antigen. In addition, PD-L1 and MHC-II were expressed on macrophages from infected animals, consistent with PD-1 and LAG-3 pathways contributing to the suppression of IFN-γ responses during the subclinical stages of M. avium subsp. paratuberculosis infection. Furthermore, dual blockade of PD-L1 and LAG-3 enhanced M. avium subsp. paratuberculosis-specific IFN-γ responses in blood from infected animals, and in vitro LAG-3 blockade enhanced IFN-γ production from M. avium subsp. paratuberculosis-specific CD4(+) and CD8(+) T cells. Taken together, the present data indicate that M. avium subsp. paratuberculosis-specific T-cell exhaustion is in part mediated by PD-1/PD-L1 and LAG-3/MHC-II interactions and that LAG-3 is a molecular target for the control of M. avium subsp. paratuberculosis-specific T-cell responses.
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