title: The Attenuated Live Yellow Fever Virus 17D Infects the Thymus and Induces Thymic Transcriptional Modifications of Immunomodulatory Genes in C57BL/6 and BALB/C Mice.
abstract: Thymus is involved in induction of self-tolerance in T lymphocytes, particularly due to Aire activity. In peripheral tissues, Treg cells and immunomodulatory molecules, like the major histocompatibility complex (MHC) class Ib molecules, are essential for maintenance of autotolerance during immune responses. Viral infections can trigger autoimmunity and modify thymic function, and YFV17D immunization has been associated with the onset of autoimmunity, being contraindicated in patients with thymic disorders. Aiming to study the influence of YFV17D immunization on the transcriptional profiles of immunomodulatory genes in thymus, we evaluated the gene expression of AIRE, FOXP3, H2-Q7 (Qa-2/HLA-G), H2-T23 (Qa-1/HLA-E), H2-Q10, and H2-K1 following immunization with 10,000 LD50 of YFV17D in C57BL/6 and BALB/c mice. The YFV17D virus replicated in thymus and induced the expression of H2-Q7 (Qa-2/HLA-G) and H2-T23 (Qa-1/HLA-E) transcripts and repressed the expression of AIRE and FOXP3. Transcriptional expression varied according to tissue and mouse strain analyzed. Expression of H2-T23 (Qa-1/HLA-E) and FOXP3 was induced in thymus and liver of C57BL/6 mice, which exhibited defective control of viral load, suggesting a higher susceptibility to YFV17D infection. Since the immunization with YFV17D modulated thymus gene expression in genetically predisposed individuals, the vaccine may be related to the onset of autoimmunity disorders.
authors.affiliation: Division of Clinical Immunology, Department of Medicine, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil ; Commissariat à l'Energie Atomique et aux Energies Alternatives, Institut des Maladies Emergentes et des Thérapies Innovantes, Service de Recherches en Hémato-Immunologie, Hôpital Saint-Louis, 1 avenue Claude Vellefaux, Bâtiment Lailler, 75475 Paris Cedex 10, France ; Université Paris-Diderot, Sorbonne Paris-Cité, UMR E5, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, 1 avenue Claude Vellefaux, 75475 Paris Cedex 10, France.
authors.forename: Breno Luiz
authors.initials: BL
authors.lastname: Melo-Lima
authors.affiliation: Virology Research Center, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil.
authors.forename: Danillo Lucas Alves
authors.initials: DL
authors.lastname: Espósito
authors.affiliation: Virology Research Center, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil.
authors.forename: Benedito Antônio Lopes
authors.initials: BA
authors.lastname: da Fonseca
authors.affiliation: Virology Research Center, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil.
authors.forename: Luiz Tadeu Moraes
authors.initials: LT
authors.lastname: Figueiredo
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives, Institut des Maladies Emergentes et des Thérapies Innovantes, Service de Recherches en Hémato-Immunologie, Hôpital Saint-Louis, 1 avenue Claude Vellefaux, Bâtiment Lailler, 75475 Paris Cedex 10, France ; Université Paris-Diderot, Sorbonne Paris-Cité, UMR E5, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, 1 avenue Claude Vellefaux, 75475 Paris Cedex 10, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.affiliation: Division of Clinical Immunology, Department of Medicine, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil.
authors.forename: Eduardo Antonio
authors.initials: EA
authors.lastname: Donadi