High proportion of PD‐1‐expressing CD4+ T cells in adipose tissue constitutes an immunomodulatory microenvironment that may support HIV persistence |
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| Authors: | Abderaouf Damouche Guillaume Pourcher Valérie Pourcher Stéphane Benoist Elodie Busson Jean‐Jacques Lataillade Mélanie Le Van Thierry Lazure Julien Adam Benoit Favier Bruno Vaslin Michaela Müller‐Trutwin Olivier Lambotte Christine Bourgeois |
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| Affiliation: | 1. Univ Paris Sud, Le Kremlin‐Bicêtre, France;2. CEA, DSV/iMETI, IDMIT, Fontenay‐aux‐Roses, France;3. Department of Digestive Diseases, Obesity center, Institut Mutualiste Montsouris, Paris‐sud University, Paris, France;4. Assistance Publique H?pitaux de Paris, H?pital Pitié‐Salpêtrière, Service de Maladies Infectieuses et Tropicales, Sorbonne Universités, France;5. Assistance Publique H?pitaux de Paris, H?pital Bicêtre, Service de Chirurgie Digestive et Oncologique, Le Kremlin‐Bicêtre, France;6. H?pital d'Instruction des Armées Percy, Centre de Transfusion Sanguine des Armées, Clamart, France;7. Assistance Publique H?pitaux de Paris, H?pital Bicêtre, Service d'anatomo‐pathologie, Le Kremlin‐Bicêtre, France;8. Institut Gustave Roussy, Plateforme d’évaluation préclinique, Villejuif, France;9. Institut Pasteur, Unité HIV, Inflammation et Persistance, Paris, France;10. Assistance Publique H?pitaux de Paris, H?pital Bicêtre, Service de Médecine Interne et Immunologie clinique, Le Kremlin‐Bicêtre, France |
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| Abstract: | We and others have demonstrated that adipose tissue is a reservoir for HIV. Evaluation of the mechanisms responsible for viral persistence may lead to ways of reducing these reservoirs. Here, we evaluated the immune characteristics of adipose tissue in HIV‐infected patients receiving antiretroviral therapy (ART) and in non‐HIV‐infected patients. We notably sought to determine whether adipose tissue's intrinsic properties and/or HIV induced alteration of the tissue environment may favour viral persistence. ART‐controlled HIV infection was associated with a difference in the CD4/CD8 T‐cell ratio and an elevated proportion of Treg cells in subcutaneous adipose tissue. No changes in Th1, Th2 and Th17 cell proportions or activation markers expression on T cell (Ki‐67, HLA‐DR) could be detected, and the percentage of CD69‐expressing resident memory CD4+ T cells was not affected. Overall, our results indicate that adipose‐tissue‐resident CD4+ T cells are not extensively activated during HIV infection. PD‐1 was expressed by a high proportion of tissue‐resident memory CD4+ T cells in both HIV‐infected patients and non‐HIV‐infected patients. Our findings suggest that adipose tissue's intrinsic immunomodulatory properties may limit immune activation and thus may strongly contribute to viral persistence. |
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| Keywords: | Adipose tissue CD4 T cell Fat HIV HIV persistence PD‐1 |
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