dc.creator | Rosado Sánchez, Isaac | es |
dc.creator | Herrero Fernández, Inés | es |
dc.creator | Sobrino, Salvador | es |
dc.creator | Carvajal, Ana Eloisa | es |
dc.creator | Genebat, Miguel | es |
dc.creator | Tarancón Díez, Laura | es |
dc.creator | Martínez de Pablos, Rocío | es |
dc.creator | Ruiz Laza, Rocío | es |
dc.creator | Leal Noval, Manuel | es |
dc.creator | Pacheco, Yolanda María | es |
dc.date.accessioned | 2024-02-26T12:19:10Z | |
dc.date.available | 2024-02-26T12:19:10Z | |
dc.date.issued | 2023-12 | |
dc.identifier.citation | Rosado Sánchez, I., Herrero Fernández, I., Sobrino, S., Carvajal, A.E., Genebat, M., Tarancón Díez, L.,...,Pacheco, Y.M. (2023). Caecum OX40+CD4 T-cell subset associates with mucosal damage and key markers of disease in treated HIV-infection. Journal of Microbiology, Immunology and Infection, 56 (6), 1129-1138. https://doi.org/10.1016/j.jmii.2023.08.011. | |
dc.identifier.issn | 1684-1182 | es |
dc.identifier.issn | 1995-9133 | es |
dc.identifier.uri | https://hdl.handle.net/11441/155590 | |
dc.description.abstract | Background
Blood OX40-expressing CD4 T-cells from antiretroviral (ART)-treated people living with HIV (PWH) were found to be enriched for clonally-expanded HIV sequences, hence contributing to the HIV reservoir. OX40-OX40L is also a checkpoint regulator of inflammation in multiple diseases. We explored gut mucosal OX40+CD4+ T-cells and their potential significance in HIV disease.
Methods
Biopsies of caecum and terminal-ileum of ART-treated PWH (n = 32) were obtained and mucosal damage and HIV reservoir were assessed. Mucosal OX40+ and Ki67+ CD4 T-cell subsets, as well as several tissue T-cell subsets modulating mucosal integrity and homeostasis (Th17, Th22, Treg, Tc17, Tc22, IL17+TCRγδ, IL22+TCRγδ) were quantified. Inflammatory-related markers, T-cell activation and thymic output were also determined in blood samples. Correlations were explored using Spearman rank test and corrected for multiple comparisons by Benjamini-Hochberg.
Results
Compared to healthy controls, a high frequency of mucosal, mainly caecum, CD4 T-cells were OX40+ in PWH. Such frequency strongly correlated with nadir CD4 (r = −0.836; p < 0.0001), CD4/CD8 ratio (r = −0.630; p = 0.002), caecum mucosal damage (r = 0.606; p = 0.008), caecum Th22 (r = −0.635; p = 0.002), caecum Th17 (r = 0.474; p = 0.03) and thymic output (r = −0.686; p < 0.001). It also correlated with Neutrophil-to-Lymphocyte Ratio and blood CD4 T-cell activation and tended to with mucosal HIV reservoir.
Conclusion
High frequencies of caecum OX40+CD4 T-cells are found in people with HIV (PWH) and successful viral control. Interestingly, this cellular subset reflects key markers of disease and peripheral T-cell activation, as well as HIV-driven mucosal damage. OX40+CD4 T-cells deserve further investigation since they could expand because of T-cell homeostatic proliferation and relate to the Th22/Th17 gut mucosal ratio. | es |
dc.description.sponsorship | Fondo de Investigación Sanitaria (FIS) de España y fondos FEDER - PI18/01216 y PI21/00357 | es |
dc.description.sponsorship | Junta de Andalucía, Consejería de Economía, Innovación, Ciencia y Empleo - CTS2593 | es |
dc.format | application/pdf | es |
dc.format.extent | 10 p. | es |
dc.language.iso | eng | es |
dc.publisher | Elsevier | es |
dc.relation.ispartof | Journal of Microbiology, Immunology and Infection, 56 (6), 1129-1138. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Caecum | es |
dc.subject | HIV | es |
dc.subject | OX40 | es |
dc.subject | Thymus | es |
dc.subject | GALT | es |
dc.title | Caecum OX40+CD4 T-cell subset associates with mucosal damage and key markers of disease in treated HIV-infection | es |
dc.type | info:eu-repo/semantics/article | es |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular | es |
dc.relation.projectID | PI18/01216 | es |
dc.relation.projectID | PI21/00357 | es |
dc.relation.projectID | CTS2593 | es |
dc.relation.publisherversion | https://doi.org/10.1016/j.jmii.2023.08.011 | es |
dc.identifier.doi | 10.1016/j.jmii.2023.08.011 | es |
dc.journaltitle | Journal of Microbiology, Immunology and Infection | es |
dc.publication.volumen | 56 | es |
dc.publication.issue | 6 | es |
dc.publication.initialPage | 1129 | es |
dc.publication.endPage | 1138 | es |
dc.contributor.funder | Fondo de Investigación Sanitaria (FIS). España | es |
dc.contributor.funder | European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER) | es |
dc.contributor.funder | Junta de Andalucía | es |