Mycobacterium tuberculosis-specific CD4 T cells expressing CD153 inversely associate with bacterial load and disease severity in human tuberculosis
| Autor: | Alan Sher, Sheena Ruzive, Alessandro Sette, Cecilia S. Lindestam Arlehamn, Robert J. Wilkinson, Daniel L. Barber, Catherine Riou, Elsa Du Bruyn |
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| Přispěvatelé: | Wellcome Trust, European and Developing Countries Clinical Trial Partnership, European and Developing Countries Clinical Trials Partnership, EDCTP |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes Male T-Cell Antigen Receptor Specificity ACTIVATION NATURAL-KILLER-CELLS 0302 clinical medicine INFECTION Immunology and Allergy Tuberculosis Vaccines Lung 11 Medical and Health Sciences IFN-GAMMA FAMILY medicine.anatomical_structure tuberculosis Tumor necrosis factor alpha Female disease severity NK CELLS MEMBERS Life Sciences & Biomedicine Adult Tuberculosis Immunology XPERT MTB/RIF ASSAY Biology Article Mycobacterium tuberculosis 03 medical and health sciences Young Adult Mediator Disease severity Active tb SCORE medicine CD4 response Animals Humans CD153 Tuberculosis Pulmonary Science & Technology HIV 06 Biological Sciences Vaccine efficacy biology.organism_classification medicine.disease Bacterial Load Disease Models Animal 030104 developmental biology CD30 Ligand 030215 immunology |
| Zdroj: | Mucosal immunology |
| ISSN: | 1935-3456 |
| Popis: | Recent data from mice and non-human primate models of tuberculosis suggested that CD153, a TNF super family member, plays an important role in Mycobacterium tuberculosis (Mtb) control. However, this molecule has not been comprehensively evaluated in humans. Here, we show that the proportion of Mtb-specific CD4 T cells expressing CD153 was significantly reduced in active TB patients compared to latently infected persons. Importantly, the CD153+ Mtb-specific CD4 response inversely correlated with lung bacterial load, inferred by Xpert cycle threshold, irrespective of HIV status. Anti-tubercular treatment partially restored CD153 expression on Mtb-specific CD4 T cells. This is the first report of a subset of Mtb-specific CD4 T cells showing strong negative correlation with bacterial burden. Building on substantial evidence from animal models implicating CD153 as a mediator of host protection, our findings suggest it may play a similar role in humans and its measurement may be useful to evaluate TB vaccine efficacy. |
| Databáze: | OpenAIRE |
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