[en] 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.
Research Center/Unit :
GIGA-I3 - Giga-Infection, Immunity and Inflammation - ULiège
Renard, Chantal; Université de Liège - ULiège > GIGA-I3
Martens, Henri ; Université de Liège - ULiège > GIGA I3 - Immunoendocrinology
Aouni, Mahjoub; Université de Monastir > Faculté de Pharmacie
Hober, Didier; Université de Lille 2 et CHRU > Laboratoire de Virologie
Geenen, Vincent ; Université de Liège - ULiège > Centre d'immunologie
Jaïdane, Hela; Université de Monastir > Faculté de Pharmacie
Language :
English
Title :
Assessment of thymic output dynamics after in utero infection of mice with coxsakievirus B4
Publication date :
02 April 2020
Journal title :
Frontiers in Immunology
eISSN :
1664-3224
Publisher :
Frontiers Research Foundation, Lausanne, Switzerland
Volume :
11
Pages :
481
Peer reviewed :
Peer Reviewed verified by ORBi
Name of the research project :
Thymus and type 1 diabetes
Funders :
MHESR - Ministère de l'Enseignement Supérieur et de la Recherche Scientifique ULiège - University of Liège
Funding text :
This work was supported by the Ministère de L’enseignement Supérieur et de la Recherche Scientifique, LR99ES27, Tunisia, and GIGA-I3 Research–Center of Immunoendocrinology, University of Liege, Belgium. AH received a mobility grant provided by the Ministère de l’Enseignement Supérieur et de la RechercheScientifique, Tunisia, also an Erasmus+ scholarship from
University of Liege.
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