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Étude des voies de génération des lymphocytes T folliculaires Helper (Tfh) humains dans un contexte pathologique d’infection par le VIH

Abstract : This thesis work aims to better characterize the generation pathways of human follicular T helpers cells (Tfh) in physiological context and pathological context of HIV infection. The generation of Tfh is mostly described as relying on the commitment of a naïve CD4+ T cells. However, the phenotypic heterogeneity within the Tfh responses allows to postulate that a Tfh cell generation pathway based on a plasticity of CD4 LT memory is possible. In order to evaluate this eventuality, we have developed a novel model of Tfh response generation based on the stimulation of human splenocytes. The resulting Tfh response shows many similarities with the one generated in lymphoid tissues following antigenic stimulation. Using this tool, we show that naïve and memory CD4+ T cells are able to orient themselves towards a Tfh profile in a lymphoid environment. Our results suggests that the heterogeneity observed in the Tfh response could rely on the contribution from different CD4+ T cell subtypes. These various generation pathways are differentially impacted with in vitro HIV infection. Combined with the analysis of splenic samples from chronically HIV-infected patients, our data provide new perspectives for the study of the processes involved in the accumulation of dysfunctional Tfh related to this pathology. More generally, this work offers a new framework for the understanding of human Tfh cell generation.
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Submitted on : Thursday, November 18, 2021 - 9:47:19 AM
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JEGER_MADIOT_Raphael_2020.pdf
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  • HAL Id : tel-03433176, version 2

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Raphaël Jeger-Madiot. Étude des voies de génération des lymphocytes T folliculaires Helper (Tfh) humains dans un contexte pathologique d’infection par le VIH. Immunologie. Sorbonne Université, 2020. Français. ⟨NNT : 2020SORUS333⟩. ⟨tel-03433176v2⟩

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