Assessment of Thymic Output Dynamics After in utero Infection of Mice With Coxsackievirus B4
The thymus is the main organ of the lymphatic system, in which T cells undergo a rigorous selection to ensure that their receptors (TCRs) will be functional and will not react against the self. Genes encoding for TCR chains are fragmented and must be rearranged by a process of somatic recombination...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.00481/full |
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| author | Aymen Halouani Aymen Halouani Aymen Halouani Habib Jmii Habib Jmii Gwennaëlle Bodart Hélène Michaux Chantal Renard Henri Martens Mahjoub Aouni Didier Hober Vincent Geenen Hela Jaïdane |
| author_facet | Aymen Halouani Aymen Halouani Aymen Halouani Habib Jmii Habib Jmii Gwennaëlle Bodart Hélène Michaux Chantal Renard Henri Martens Mahjoub Aouni Didier Hober Vincent Geenen Hela Jaïdane |
| author_sort | Aymen Halouani |
| collection | DOAJ |
| description | The thymus is the main organ of the lymphatic system, in which T cells undergo a rigorous selection to ensure that their receptors (TCRs) will be functional and will not react against the self. Genes encoding for TCR chains are fragmented and must be rearranged by a process of somatic recombination generating TCR rearrangement excision circles (TRECs). We recently documented coxsackievirus B4 (CV-B4) infection of Swiss albino mouse thymus in the course of in utero transmission. In the current study, we intended to evaluate thymic output in this experimental model. For this purpose, pregnant Swiss albino mice were inoculated with CV-B4 at day 10 or 17 of gestation, and thymus and spleen were sampled from offspring at different time points and then subjected to quantification of TREC molecules and Ptk7 gene expression. Results showed a pronounced effect of in utero CV-B4 infection on the thymus with an increase in the cellularity and, consequently, the weight of the organ. sj and DβTREC analysis, by real-time PCR, revealed a significant decrease following CV-B4 infection compared to controls, a decrease which gets worse as time goes by, both in the thymus and in the periphery. Those observations reflect a disturbance in the export of T cells to the periphery and their accumulation within the thymus. The evaluation of Ptk7 transcripts in the thymus, for its part, showed a decrease in expression, especially following an infection at day 10 of gestation, which supports the hypothesis of T cell accumulation in a mature stage in the thymus. The various effects observed correlate either negatively or positively with the viral load in the thymus and spleen. Disruption in thymic export may indeed interfere with T cell maturation. We speculate that this may lead to a premature release of T cells and the possibility of circulating autoreactive or proliferation-impaired T cell clones. |
| first_indexed | 2024-12-22T08:30:42Z |
| format | Article |
| id | doaj.art-454265833b714b7f833cb221d4f79f86 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-22T08:30:42Z |
| publishDate | 2020-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-454265833b714b7f833cb221d4f79f862022-12-21T18:32:30ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-04-011110.3389/fimmu.2020.00481507750Assessment of Thymic Output Dynamics After in utero Infection of Mice With Coxsackievirus B4Aymen Halouani0Aymen Halouani1Aymen Halouani2Habib Jmii3Habib Jmii4Gwennaëlle Bodart5Hélène Michaux6Chantal Renard7Henri Martens8Mahjoub Aouni9Didier Hober10Vincent Geenen11Hela Jaïdane12Laboratoire des Maladies Transmissibles et Substances Biologiquement Actives, Faculté de Pharmacie de Monastir, Université de Monastir, Monastir, TunisiaFaculté des Sciences de Tunis, Université de Tunis El Manar, Tunis, TunisiaGIGA-I3 Neuroimmunoendocrinology, GIGA Research Institute, University of Liège, Liège, BelgiumLaboratoire des Maladies Transmissibles et Substances Biologiquement Actives, Faculté de Pharmacie de Monastir, Université de Monastir, Monastir, TunisiaFaculté des Sciences de Tunis, Université de Tunis El Manar, Tunis, TunisiaGIGA-I3 Neuroimmunoendocrinology, GIGA Research Institute, University of Liège, Liège, BelgiumGIGA-I3 Neuroimmunoendocrinology, GIGA Research Institute, University of Liège, Liège, BelgiumGIGA-I3 Neuroimmunoendocrinology, GIGA Research Institute, University of Liège, Liège, BelgiumGIGA-I3 Neuroimmunoendocrinology, GIGA Research Institute, University of Liège, Liège, BelgiumLaboratoire des Maladies Transmissibles et Substances Biologiquement Actives, Faculté de Pharmacie de Monastir, Université de Monastir, Monastir, TunisiaUniversité de Lille, CHU de Lille, Laboratoire de Virologie, Lille, FranceGIGA-I3 Neuroimmunoendocrinology, GIGA Research Institute, University of Liège, Liège, BelgiumLaboratoire des Maladies Transmissibles et Substances Biologiquement Actives, Faculté de Pharmacie de Monastir, Université de Monastir, Monastir, TunisiaThe thymus is the main organ of the lymphatic system, in which T cells undergo a rigorous selection to ensure that their receptors (TCRs) will be functional and will not react against the self. Genes encoding for TCR chains are fragmented and must be rearranged by a process of somatic recombination generating TCR rearrangement excision circles (TRECs). We recently documented coxsackievirus B4 (CV-B4) infection of Swiss albino mouse thymus in the course of in utero transmission. In the current study, we intended to evaluate thymic output in this experimental model. For this purpose, pregnant Swiss albino mice were inoculated with CV-B4 at day 10 or 17 of gestation, and thymus and spleen were sampled from offspring at different time points and then subjected to quantification of TREC molecules and Ptk7 gene expression. Results showed a pronounced effect of in utero CV-B4 infection on the thymus with an increase in the cellularity and, consequently, the weight of the organ. sj and DβTREC analysis, by real-time PCR, revealed a significant decrease following CV-B4 infection compared to controls, a decrease which gets worse as time goes by, both in the thymus and in the periphery. Those observations reflect a disturbance in the export of T cells to the periphery and their accumulation within the thymus. The evaluation of Ptk7 transcripts in the thymus, for its part, showed a decrease in expression, especially following an infection at day 10 of gestation, which supports the hypothesis of T cell accumulation in a mature stage in the thymus. The various effects observed correlate either negatively or positively with the viral load in the thymus and spleen. Disruption in thymic export may indeed interfere with T cell maturation. We speculate that this may lead to a premature release of T cells and the possibility of circulating autoreactive or proliferation-impaired T cell clones.https://www.frontiersin.org/article/10.3389/fimmu.2020.00481/fullthymusT cellthymic exportT cell receptor (TCR) rearrangement excision circlesautoimmune diseasesPtk7 gene |
| spellingShingle | Aymen Halouani Aymen Halouani Aymen Halouani Habib Jmii Habib Jmii Gwennaëlle Bodart Hélène Michaux Chantal Renard Henri Martens Mahjoub Aouni Didier Hober Vincent Geenen Hela Jaïdane Assessment of Thymic Output Dynamics After in utero Infection of Mice With Coxsackievirus B4 Frontiers in Immunology thymus T cell thymic export T cell receptor (TCR) rearrangement excision circles autoimmune diseases Ptk7 gene |
| title | Assessment of Thymic Output Dynamics After in utero Infection of Mice With Coxsackievirus B4 |
| title_full | Assessment of Thymic Output Dynamics After in utero Infection of Mice With Coxsackievirus B4 |
| title_fullStr | Assessment of Thymic Output Dynamics After in utero Infection of Mice With Coxsackievirus B4 |
| title_full_unstemmed | Assessment of Thymic Output Dynamics After in utero Infection of Mice With Coxsackievirus B4 |
| title_short | Assessment of Thymic Output Dynamics After in utero Infection of Mice With Coxsackievirus B4 |
| title_sort | assessment of thymic output dynamics after in utero infection of mice with coxsackievirus b4 |
| topic | thymus T cell thymic export T cell receptor (TCR) rearrangement excision circles autoimmune diseases Ptk7 gene |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.00481/full |
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