Artículo
Caecum OX40+CD4 T-cell subset associates with mucosal damage and key markers of disease in treated HIV-infection
Autor/es | Rosado Sánchez, Isaac
Herrero Fernández, Inés Sobrino, Salvador Carvajal, Ana Eloisa Genebat, Miguel Tarancón Díez, Laura Martínez de Pablos, Rocío Ruiz Laza, Rocío Leal Noval, Manuel Pacheco, Yolanda María |
Departamento | Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular |
Fecha de publicación | 2023-12 |
Fecha de depósito | 2024-02-26 |
Publicado en |
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Resumen | 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 ... 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. |
Agencias financiadoras | Fondo de Investigación Sanitaria (FIS). España European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER) Junta de Andalucía |
Identificador del proyecto | PI18/01216
PI21/00357 CTS2593 |
Cita | 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. |
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