Cooperation of PD-1 and LAG-3 Contributes to T-Cell Exhaustion in Anaplasma marginale-Infected Cattle
Rattachement africain : jp, us. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
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.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Cooperation of PD-1 and LAG-3 Contributes to T-Cell Exhaustion in Anaplasma marginale-Infected Cattle
- Date Crossref
- 01/10/2016
- Éditeur
- American Society for Microbiology
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Hokkaido University pays non établi dans la noticeUniversité ou école supérieure
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Washington State University Department of Veterinary Microbiology and Pathology pays non établi dans la noticeUniversité ou école supérieure
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Agricultural Research Service pays non établi dans la noticeOrganisme public
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United States Department of Agriculture pays non établi dans la noticeOrganisme public
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Graduate School of Veterinary Medicine Department of Disease Control pays non établi dans la noticeUniversité ou école supérieure
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Animal Disease Research Unit pays non établi dans la noticeStructure de recherche
Hokkaido University, Department of Veterinary Microbiology and Pathology — Washington State University et Agricultural Research Service, avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.