SARS-COV-2 specific t-cells in patients with thyroid disorders related to COVID-19 are enriched in the thyroid and acquire a tissue-resident memory phenotype.

Autor: Silvestri Y; Istituto Nazionale Genetica Molecolare Romeo ed Enrica Invernizzi, Milan, Italy., Clemente F; Istituto Nazionale Genetica Molecolare Romeo ed Enrica Invernizzi, Milan, Italy., Moschetti G; Istituto Nazionale Genetica Molecolare Romeo ed Enrica Invernizzi, Milan, Italy., Maioli S; Dipartimento di Scienze Cliniche e di Comunità, Università di Milano, Milan, Italy., Carelli E; Istituto Nazionale Genetica Molecolare Romeo ed Enrica Invernizzi, Milan, Italy., Espadas de Arias A; S.C. Trapianti Lombardia - NITp, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Via Sforza 35 c/o INGM, 20122 Milano, Iraly., Torelli R; S.C. Trapianti Lombardia - NITp, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Via Sforza 35 c/o INGM, 20122 Milano, Iraly., Longhi E; S.C. Trapianti Lombardia - NITp, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Via Sforza 35 c/o INGM, 20122 Milano, Iraly., De Feo T; S.C. Trapianti Lombardia - NITp, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Via Sforza 35 c/o INGM, 20122 Milano, Iraly., Crosti M; Istituto Nazionale Genetica Molecolare Romeo ed Enrica Invernizzi, Milan, Italy., Sarnicola ML; Istituto Nazionale Genetica Molecolare Romeo ed Enrica Invernizzi, Milan, Italy., Salvi M; Struttura Complessa Endocrinologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Mantovani G; Dipartimento di Scienze Cliniche e di Comunità, Università di Milano, Milan, Italy; Struttura Complessa Endocrinologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Arosio M; Dipartimento di Scienze Cliniche e di Comunità, Università di Milano, Milan, Italy; Struttura Complessa Endocrinologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Bombaci M; Istituto Nazionale Genetica Molecolare Romeo ed Enrica Invernizzi, Milan, Italy., Pesce E; Istituto Nazionale Genetica Molecolare Romeo ed Enrica Invernizzi, Milan, Italy., Grifantini R; Istituto Nazionale Genetica Molecolare Romeo ed Enrica Invernizzi, Milan, Italy., Abrignani S; Istituto Nazionale Genetica Molecolare Romeo ed Enrica Invernizzi, Milan, Italy; Dipartimento di Scienze Cliniche e di Comunità, Università di Milano, Milan, Italy., Geginat J; Istituto Nazionale Genetica Molecolare Romeo ed Enrica Invernizzi, Milan, Italy; Dipartimento di Scienze Cliniche e di Comunità, Università di Milano, Milan, Italy., Muller I; Dipartimento di Scienze Cliniche e di Comunità, Università di Milano, Milan, Italy; Struttura Complessa Endocrinologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Jazyk: angličtina
Zdroj: Clinical immunology (Orlando, Fla.) [Clin Immunol] 2023 Sep; Vol. 254, pp. 109684. Date of Electronic Publication: 2023 Jul 13.
DOI: 10.1016/j.clim.2023.109684
Abstrakt: Background: SARS-CoV-2 infections have been associated with the onset of thyroid disorders like classic subacute thyroiditis (SAT) or atypical SAT upon severe COVID disease (COV-A-SAT). Little is known about thyroid anti-viral immune responses.
Objectives: To define the role of T-cells in COV-A-SAT.
Methods: T-cells from COV-A-SAT patients were analyzed by multi-dimensional flow cytometry, UMAP and DiffusionMap dimensionality reduction and FlowSOM clustering. T-cells from COVID-naïve healthy donors, patients with autoimmune thyroiditis (ATD) and with SAT following COVID vaccination were analyzed as controls. T-cells were analyzed four and eight months post-infection in peripheral blood and in thyroid specimen obtained by ultrasound-guided fine needle aspiration. SARS-COV2-specific T-cells were identified by cytokine production induced by SARS-COV2-derived peptides and with COVID peptide-loaded HLA multimers after HLA haplotyping.
Results: COV-A-SAT was associated with HLA-DRB1*13 and HLA-B*57. COV-A-SAT patients contained activated Th1- and cytotoxic CD4+ and CD8+ effector cells four months post-infection, which acquired a quiescent memory phenotype after eight months. Anti-SARS-CoV-2-specific T-cell responses were readily detectable in peripheral blood four months post-infection, but were reduced after eight months. CD4+ and CD8+ tissue-resident memory cells (TRM) were present in the thyroid, and circulating CXCR3+T-cells identified as their putative precursors. SARS-CoV-2-specific T-cells were enriched in the thyroid, and acquired a TRM phenotype eight months post-infection.
Conclusions: The association of COV-A-SAT with specific HLA haplotypes suggests a genetic predisposition and a key role for T-cells. COV-A-SAT is characterized by a prolonged systemic anti-viral effector T-cell response and the late generation of COVID-specific TRM in the thyroid target tissue.
Competing Interests: Declaration of Competing Interest We declare no conflict of interest.
(Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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