دورية أكاديمية
Recently activated CD4 T cells in tuberculosis express OX40 as a target for host-directed immunotherapy.
| العنوان: | Recently activated CD4 T cells in tuberculosis express OX40 as a target for host-directed immunotherapy. |
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| المؤلفون: | Gress AR; Department of Medicine, University of Minnesota, 420 Delaware Street, SE MMC 250, Minneapolis, MN, 55455, USA.; Center for Immunology, 2101 6th St SE, WMBB 2-118, University of Minnesota, Minneapolis, MN, 55455, USA., Ronayne CE; Department of Medicine, University of Minnesota, 420 Delaware Street, SE MMC 250, Minneapolis, MN, 55455, USA.; Center for Immunology, 2101 6th St SE, WMBB 2-118, University of Minnesota, Minneapolis, MN, 55455, USA., Thiede JM; Department of Medicine, University of Minnesota, 420 Delaware Street, SE MMC 250, Minneapolis, MN, 55455, USA.; Center for Immunology, 2101 6th St SE, WMBB 2-118, University of Minnesota, Minneapolis, MN, 55455, USA., Meyerholz DK; Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, 1165 Medical Laboratories (ML), 51 Newton Rd, University of Iowa, Iowa City, IA, 52242, USA., Okurut S; Infectious Diseases Institute, P.O. Box 22418, Makerere University, Kampala, Uganda., Stumpf J; Department of Medicine, University of Minnesota, 420 Delaware Street, SE MMC 250, Minneapolis, MN, 55455, USA., Mathes TV; Department of Medicine, University of Minnesota, 420 Delaware Street, SE MMC 250, Minneapolis, MN, 55455, USA.; Center for Immunology, 2101 6th St SE, WMBB 2-118, University of Minnesota, Minneapolis, MN, 55455, USA., Ssebambulidde K; Infectious Diseases Institute, P.O. Box 22418, Makerere University, Kampala, Uganda., Meya DB; Infectious Diseases Institute, P.O. Box 22418, Makerere University, Kampala, Uganda., Cresswell FV; Infectious Diseases Institute, P.O. Box 22418, Makerere University, Kampala, Uganda.; MRC/UVRI and London School of Hygiene and Tropical Medicine Uganda Research Unit, PO Box 49, Plot 51-59, Nakiwogo Road Entebbe, Entebbe, Uganda.; Department of Global Health and Infection, Brighton and Sussex Medical School, Brighton, East Sussex, BN1 9PX, UK., Boulware DR; Department of Medicine, University of Minnesota, 420 Delaware Street, SE MMC 250, Minneapolis, MN, 55455, USA., Bold TD; Department of Medicine, University of Minnesota, 420 Delaware Street, SE MMC 250, Minneapolis, MN, 55455, USA. tbold@umn.edu.; Center for Immunology, 2101 6th St SE, WMBB 2-118, University of Minnesota, Minneapolis, MN, 55455, USA. tbold@umn.edu. |
| المصدر: | Nature communications [Nat Commun] 2023 Dec 19; Vol. 14 (1), pp. 8423. Date of Electronic Publication: 2023 Dec 19. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [London] : Nature Pub. Group |
| مواضيع طبية MeSH: | CD4-Positive T-Lymphocytes* , Tuberculosis*/therapy, Humans ; Mice ; Animals ; Receptors, OX40/agonists ; CD8-Positive T-Lymphocytes ; Immunotherapy |
| مستخلص: | After Mycobacterium tuberculosis (Mtb) infection, many effector T cells traffic to the lungs, but few become activated. Here we use an antigen receptor reporter mouse (Nur77-GFP) to identify recently activated CD4 T cells in the lungs. These Nur77-GFP HI cells contain expanded TCR clonotypes, have elevated expression of co-stimulatory genes such as Tnfrsf4/OX40, and are functionally more protective than Nur77-GFP LO cells. By contrast, Nur77-GFP LO cells express markers of terminal exhaustion and cytotoxicity, and the trafficking receptor S1pr5, associated with vascular localization. A short course of immunotherapy targeting OX40 + cells transiently expands CD4 T cell numbers and shifts their phenotype towards parenchymal protective cells. Moreover, OX40 agonist immunotherapy decreases the lung bacterial burden and extends host survival, offering an additive benefit to antibiotics. CD4 T cells from the cerebrospinal fluid of humans with HIV-associated tuberculous meningitis commonly express surface OX40 protein, while CD8 T cells do not. Our data thus propose OX40 as a marker of recently activated CD4 T cells at the infection site and a potential target for immunotherapy in tuberculosis. (© 2023. The Author(s).) |
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| معلومات مُعتمدة: | T32 AI007313 United States AI NIAID NIH HHS; L30 AI140336 United States AI NIAID NIH HHS; T32 HL007741 United States HL NHLBI NIH HHS; R01 AI162786 United States AI NIAID NIH HHS; R01 AI173780 United States AI NIAID NIH HHS; MR/S004963/1 United Kingdom MRC_ Medical Research Council; T32 AI055433 United States AI NIAID NIH HHS; K08 AI150425 United States AI NIAID NIH HHS |
| المشرفين على المادة: | 0 (Receptors, OX40) |
| تواريخ الأحداث: | Date Created: 20231218 Date Completed: 20231220 Latest Revision: 20240620 |
| رمز التحديث: | 20240620 |
| مُعرف محوري في PubMed: | PMC10728168 |
| DOI: | 10.1038/s41467-023-44152-8 |
| PMID: | 38110410 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 2041-1723 |
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| DOI: | 10.1038/s41467-023-44152-8 |