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Seminar

Friday, November 29th, 2019
11h
Centre de Recherche - Paris - Amphith√©√Ętre Constant Burg, Salle annexe 1

Role of T follicular helper cells in HIV-1 persistence

Increasing number of evidences indicate that B-cell follicles might be anatomical sanctuaries for active and persistent transcription in both HIV/SIV viremic controllers and in ART treated aviremic HIV-infected individuals and have underscored the importance of the delineation of mechanisms allowing viral persistence in lymph nodes (LNs) to ultimately eradicate or functionally cure HIV.

While multiple mechanisms may be involved in the regulation of HIV transcription, recent studies suggest that immune checkpoint (IC) molecule expression may contribute to control HIV-1 transcription and therefore maintain HIV-1 latency in HIV-infected memory CD4 T cells. We therefore hypothesized that IC/IC-ligand (IC-L) interactions may contribute to modulate HIV latency/virus reactivation in LN microenvironment.

In the present study, we demonstrate that PD-1 and TIGIT, the two major ICs expressed on T follicular helper (Tfh) cells ex vivo, are functionally active and regulate TCR-mediated HIV-1 transcription and production in vitro. However, PD-L1 (PD-1-ligand) and CD155 (TIGIT-ligand), predominantly co-expressed on LN migratory dendritic cells (DCs), preponderantly locate in extra-follicular areas of ART treated subjects, suggesting that IC/IC-L interactions might be selectively reduced in germinal centers (GCs) of ART-treated subjects. Interestingly, we show that LN migratory DCs could modulate TCR-mediated HIV-1 production from LN PD-1+/Tfh cells of ART treated HIV-infected individuals by a mechanism involving PD-L1-2/PD-1 interactions.

These results indicate that LN migratory DCs expressing IC-Ls may more efficiently restrict HIV-1 transcription in the extra-follicular areas versus GCs and explain the persistent HIV transcription in PD-1+/Tfh cells after prolonged ART.

Speaker(s)

Matthieu Perreau
PhD

Lausanne University Hospital, Lausanne, Switzerland

Invited by

Nicolas Manel
Domain 3 - U932 - Immunity and Cancer

Institut Curie

Philippe Benaroch
Domain 3 - U932 - Immunity and Cancer

Institut Curie

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Nicolas Manel

Institut Curie

Philippe Benaroch

Institut Curie

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