Study of CD4+ T cell/ B cell interactions in Long COVID

Responsable du Stage : Dr Lisa CHAKRABARTI

Tél : 01 45 68 89 45        E-mail:

Institut Pasteur

Résumé du Projet de Stage 

A significant proportion of patients with COVID-19 still experience symptoms such as profound fatigue, neurocognitive impairment (« brain fog »), and chest pains more than 3 months after an initial infection with SARS-CoV-2. The persistence of these debilitating symptoms defines the Long COVID syndrome, which has gained recognition through patient advocacy, and is now considered a serious public health concern. Importantly, the etiology of Long COVID remains unknown. We propose to test the hypothesis that a weak antiviral immune response underlies Long COVID, which may account for cases of viral persistence that have recently reported in Long COVID patients.
The project will first involve a comparison of the nature of the antiviral T cell responses in Long Covid patients and patients cured of COVID, using intracellular cytokine staining and activation-induced marker (AIM) assays. The student will then explore possible bias in B cell / CD4+ T cell interactions, and test in particular the notion that decreased T follicular helper (Tfh) function may account for the low or undetectable SARS-CoV-2 antibody levels often reported in Long COVID patients. The student will take advantage of a recently developed model of lymph node-on-chip to analyze Tfh/ B cell interactions in a 3D environment after trimeric S protein stimulation. The formation of CD4+ T cell/ B cell aggregates will be monitored in the microfluidics chip by fluorescence imaging, and the production of antibodies will be monitored in the effluent of the chip. In addition, plasmablast formation will be monitored by flow cytometry after recovery of the cells within the chip. Further approaches will aim at testing in vitro vaccination strategies that could help restore functional Tfh/B cell interactions in cells from Long Covid patients.

Dernières Publications en lien avec le projet :

(1) – Robinot R., Hubert M., … , Michel V.*, Schwartz O.*, and Chakrabarti L.A.* (2021) SARS-CoV-2 infection damages airway motile cilia and impairs mucociliary clearance. Nature Communications, in press; Preprint :
(2) – Galperin M, Farenc C, … , Rossjohn J*, Chakrabarti LA*, and Gras S* (2018) CD4+ T cell mediated HLA class II cross-restriction in HIV controllers. Science Immunology 2018 Jun 8;3(24) pii: eaat0687
(3) – Claireaux M, Galperin M, … , Moog C, Lambotte O, and Chakrabarti LA* (2018) High frequency of HIVspecific circulating follicular helper T cells associates with preserved memory B cell responses in HIV controllers. mBio 2018 May 8;9(3) pii: 9:e00317-18
(4) Benati *, Galperin M, …, Delfraissy JF, Arenzana-Seisdedos F, and Chakrabarti LA* (2016) Public TCRs confer high-avidity CD4 responses to HIV Controllers. Journal of Clinical Investigation 26:2093-2108
(5) – Mukhopadhyay M., Galperin M., … , Lambotte O., Huang Y., and Chakrabarti L.A. (2017) DNA vaccination by electroporation amplifies broadly cross-restricted public TCR clonotypes shared with HIV controllers. Journal of Immunology 199: 3437-3452.

Ce projet s’inscrit-il dans la perspective d’une thèse :
oui X

ED d’appartenance : ED BioSPC

Chakrabarti_FicheaccueilM2-BMC-2021-2022 (1)

Equipes d’Accueil : Groupe Contrôle des Infections Virales Chroniques (CIVIC)

Intitulé de l’Unité : Unité Virus et Immunité

Nom du Responsable de l’Unité : Pr Olivier SCHWARTZ
Nom du Responsable de l’Équipe : Dr Lisa CHAKRABARTI

Institut Pasteur, 28 rue du Dr Roux, 75724 PARIS CEDEX 15