Narcolepsy Type 1 Is Associated with a Systemic Increase and Activation of Regulatory T Cells and with a Systemic Activation of Global T Cells
Identifieur interne : 000250 ( Main/Exploration ); précédent : 000249; suivant : 000251Narcolepsy Type 1 Is Associated with a Systemic Increase and Activation of Regulatory T Cells and with a Systemic Activation of Global T Cells
Auteurs : Michel Lecendreux [France] ; Guillaume Churlaud [France] ; Fabien Pitoiset [France] ; Armelle Regnault [France] ; Tu Anh Tran [France] ; Roland Liblau [France] ; David Klatzmann [France] ; Michelle Rosenzwajg [France]Source :
- PLoS ONE [ 1932-6203 ] ; 2017-01-20.
Abstract
Narcolepsy is a rare neurologic disorder characterized by excessive daytime sleepiness, cataplexy and disturbed nocturnal sleep patterns. Narcolepsy type 1 (NT1) has been shown to result from a selective loss of hypothalamic hypocretin-secreting neurons with patients typically showing low CSF-hypocretin levels (<110 pg/ml). This specific loss of hypocretin and the strong association with the HLA-DQB1*06:02 allele led to the hypothesis that NT1 could be an immune-mediated pathology. Moreover, susceptibility to NT1 has recently been associated with several pathogens, particularly with influenza A H1N1 virus either through infection or vaccination. The goal of this study was to compare peripheral blood immune cell populations in recent onset pediatric NT1 subjects (post or non-post 2009-influenza A H1N1 vaccination) to healthy donors. We demonstrated an increased number of central memory CD4 + T cells (CD62L + CD45RA-) associated to an activated phenotype (increase in CD69 and CD25 expression) in NT1 patients. Percentage and absolute count of regulatory T cells (Tregs) in NT1 patients were increased associated with an activated phenotype (increase in GITR and LAP expression), and of activated memory phenotype. Cytokine production by CD4 + and CD8 + T cells after activation was not modified in NT1 patients. In H1N1 vaccinated NT1 patients, absolute counts of CD3 + , CD8 + T cells, and B cells were increased compared to non-vaccinated NT1 patients. These results support a global T cell activation in NT1 patients and thus support a T cell-mediated autoimmune origin of NT1, but do not demonstrate the pathological role of H1N1 prophylactic vaccination. They should prompt further studies of T cells, particularly of Tregs (such as suppression and proliferation antigen specific assays, and also T-cell receptor sequencing), in NT1.
Url:
DOI: 10.1371/journal.pone.0169836
Affiliations:
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<author><name sortKey="Klatzmann, David" sort="Klatzmann, David" uniqKey="Klatzmann D" first="David" last="Klatzmann">David Klatzmann</name>
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<author><name sortKey="Rosenzwajg, Michelle" sort="Rosenzwajg, Michelle" uniqKey="Rosenzwajg M" first="Michelle" last="Rosenzwajg">Michelle Rosenzwajg</name>
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<idno type="DOI">10.1371/journal.pone.0169836</idno>
<series><title level="j">PLoS ONE</title>
<idno type="ISSN">1932-6203</idno>
<imprint><date type="datePub">2017-01-20</date>
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<front><div type="abstract" xml:lang="en"> <p>Narcolepsy is a rare neurologic disorder characterized by excessive daytime sleepiness, cataplexy and disturbed nocturnal sleep patterns. Narcolepsy type 1 (NT1) has been shown to result from a selective loss of hypothalamic hypocretin-secreting neurons with patients typically showing low CSF-hypocretin levels (<110 pg/ml). This specific loss of hypocretin and the strong association with the HLA-DQB1*06:02 allele led to the hypothesis that NT1 could be an immune-mediated pathology. Moreover, susceptibility to NT1 has recently been associated with several pathogens, particularly with influenza A H1N1 virus either through infection or vaccination. The goal of this study was to compare peripheral blood immune cell populations in recent onset pediatric NT1 subjects (post or non-post 2009-influenza A H1N1 vaccination) to healthy donors. We demonstrated an increased number of central memory CD4 + T cells (CD62L + CD45RA-) associated to an activated phenotype (increase in CD69 and CD25 expression) in NT1 patients. Percentage and absolute count of regulatory T cells (Tregs) in NT1 patients were increased associated with an activated phenotype (increase in GITR and LAP expression), and of activated memory phenotype. Cytokine production by CD4 + and CD8 + T cells after activation was not modified in NT1 patients. In H1N1 vaccinated NT1 patients, absolute counts of CD3 + , CD8 + T cells, and B cells were increased compared to non-vaccinated NT1 patients. These results support a global T cell activation in NT1 patients and thus support a T cell-mediated autoimmune origin of NT1, but do not demonstrate the pathological role of H1N1 prophylactic vaccination. They should prompt further studies of T cells, particularly of Tregs (such as suppression and proliferation antigen specific assays, and also T-cell receptor sequencing), in NT1.</p>
</div>
</front>
</TEI>
<affiliations><list><country><li>France</li>
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<tree><country name="France"><noRegion><name sortKey="Lecendreux, Michel" sort="Lecendreux, Michel" uniqKey="Lecendreux M" first="Michel" last="Lecendreux">Michel Lecendreux</name>
</noRegion>
<name sortKey="Churlaud, Guillaume" sort="Churlaud, Guillaume" uniqKey="Churlaud G" first="Guillaume" last="Churlaud">Guillaume Churlaud</name>
<name sortKey="Klatzmann, David" sort="Klatzmann, David" uniqKey="Klatzmann D" first="David" last="Klatzmann">David Klatzmann</name>
<name sortKey="Liblau, Roland" sort="Liblau, Roland" uniqKey="Liblau R" first="Roland" last="Liblau">Roland Liblau</name>
<name sortKey="Pitoiset, Fabien" sort="Pitoiset, Fabien" uniqKey="Pitoiset F" first="Fabien" last="Pitoiset">Fabien Pitoiset</name>
<name sortKey="Regnault, Armelle" sort="Regnault, Armelle" uniqKey="Regnault A" first="Armelle" last="Regnault">Armelle Regnault</name>
<name sortKey="Rosenzwajg, Michelle" sort="Rosenzwajg, Michelle" uniqKey="Rosenzwajg M" first="Michelle" last="Rosenzwajg">Michelle Rosenzwajg</name>
<name sortKey="Tran, Tu Anh" sort="Tran, Tu Anh" uniqKey="Tran T" first="Tu Anh" last="Tran">Tu Anh Tran</name>
</country>
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