mTOR Inhibitors Prevent CMV Infection through the Restoration of Functional αβ and γδ T cells in Kidney Transplantation
In: Journal of the American Society of Nephrology Journal of the American Society of Nephrology, American Society of Nephrology, 2021, ⟨10.1681/ASN.2020121753⟩ Journal of the American Society of Nephrology, inPress, pp.121-137. ⟨10.1681/ASN.2020121753⟩ Journal of the American Society of Nephrology, 2021, ⟨10.1681/ASN.2020121753⟩ J Am Soc Nephrol Journal of the American Society of Nephrology, American Society of Nephrology, In press, pp.ASN.2020121753. ⟨10.1681/ASN.2020121753⟩ Journal of the American Society of Nephrology, 2021, 33 (1), pp.121-137. ⟨10.1681/ASN.2020121753⟩; (2021-11-01)
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Zugriff:
International audience; Background The reported association of mTOR-inhibitor (mTORi) treatment with a lower incidence of cytomegalovirus (CMV) infection in kidney transplant recipients (KTR) who are CMV seropositive (R+) remains unexplained. Methods The incidence of CMV infection and T-cell profile was compared between KTRs treated with mTORis and mycophenolic acid (MPA), and in vitro mTORi effects on T-cell phenotype and functions were analyzed. Results In KTRs who were R+ and treated with MPA, both αβ and γδ T cells displayed a more dysfunctional phenotype (PD-1+, CD85j+) at day 0 of transplantation in the 16 KTRs with severe CMV infection, as compared with the 17 KTRs without or with spontaneously resolving CMV infection. In patients treated with mTORis ( n =27), the proportion of PD-1+ and CD85j+ αβ and γδ T cells decreased, when compared with patients treated with MPA ( n =44), as did the frequency and severity of CMV infections. mTORi treatment also led to higher proportions of late-differentiated and cytotoxic γδ T cells and IFN γ -producing and cytotoxic αβ T cells. In vitro , mTORis increased proliferation, viability, and CMV-induced IFN γ production of T cells and decreased PD-1 and CD85j expression in T cells, which shifted the T cells to a more efficient EOMES low Hobit high profile. In γδ T cells, the mTORi effect was related to increased TCR signaling. Conclusion Severe CMV replication is associated with a dysfunctional T-cell profile and mTORis improve T-cell fitness along with better control of CMV. A dysfunctional T-cell phenotype could serve as a new biomarker to predict post-transplantation infection and to stratify patients who should benefit from mTORi treatment. Clinical Trial registry name and registration number: Proportion of CMV Seropositive Kidney Transplant Recipients Who Will Develop a CMV Infection When Treated With an Immunosuppressive Regimen Including Everolimus and Reduced Dose of Cyclosporine Versus an Immunosuppressive Regimen With Mycophenolic Acid and Standard Dose of Cyclosporine A (EVERCMV), NCT02328963
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mTOR Inhibitors Prevent CMV Infection through the Restoration of Functional αβ and γδ T cells in Kidney Transplantation
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Autor/in / Beteiligte Person: | Garrigue, Isabelle ; Yared, Nathalie ; Merville, Pierre ; Couzi, Lionel ; Nokin, Marie-Julie ; Capone, Myriam ; Mamani, Maria ; Pitard, Vincent ; Durán, Raúl V. ; Coueron, Roxane ; Pinson, Benoît ; Gauthereau, Xavier ; Marsères, Gabriel ; Déchanet-Merville, Julie ; Loizon, Séverine ; Pellegrin, Isabelle ; Zouine, Atika ; Kaminski, Hannah ; Thiébaut, Rodolphe ; Immunology from Concept and Experiments to Translation (ImmunoConcept) ; Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB) ; Microbiologie cellulaire et moléculaire et pathogénicité (MCMP) ; Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS) ; Transbiomed : Biologie Fondamentale et Appliquée à la Médecine ; Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM) ; Bordeaux population health (BPH) ; Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM) ; Institut de biochimie et génétique cellulaires (IBGC) ; CHU Bordeaux [Bordeaux] ; Statistics In System biology and Translational Medicine (SISTM) ; Inria Bordeaux - Sud-Ouest ; Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)- Bordeaux population health (BPH) ; Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM) ; ANR-19-CE18-0024,TEPEE,Conjugués polymersomes-cellules T bio-inspirés et biomimétiques: un concept biohybride combinant thérapie cellulaire et vectorisation(2019) ; Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS) ; Composantes innées de la réponse immunitaire et différenciation (CIRID) ; Institut Européen de Chimie et Biologie (IECB) ; Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) ; Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION) ; Institut Bergonié [Bordeaux] ; UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM) ; TBM-Core [Bordeaux] (UMS3427 - INSERM US005) ; Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) ; Microbiologie Fondamentale et Pathogénicité (MFP) ; Université de Bordeaux (UB) ; Admin, Oskar ; Conjugués polymersomes-cellules T bio-inspirés et biomimétiques: un concept biohybride combinant thérapie cellulaire et vectorisation - - TEPEE2019 - ANR-19-CE18-0024 - AAPG2019 -, VALID ; PINSON, Benoît ; TBM-Core [Bordeaux] (CNRS UMS 3427 - INSERM US 005) |
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Quelle: | Journal of the American Society of Nephrology Journal of the American Society of Nephrology, American Society of Nephrology, 2021, ⟨10.1681/ASN.2020121753⟩ Journal of the American Society of Nephrology, inPress, pp.121-137. ⟨10.1681/ASN.2020121753⟩ Journal of the American Society of Nephrology, 2021, ⟨10.1681/ASN.2020121753⟩ J Am Soc Nephrol Journal of the American Society of Nephrology, American Society of Nephrology, In press, pp.ASN.2020121753. ⟨10.1681/ASN.2020121753⟩ Journal of the American Society of Nephrology, 2021, 33 (1), pp.121-137. ⟨10.1681/ASN.2020121753⟩; (2021-11-01) |
Veröffentlichung: | HAL CCSD, 2021 |
Medientyp: | unknown |
ISSN: | 1046-6673 (print) ; 1533-3450 (print) |
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