CD32⁺ and PD-1⁺ Lymph Node CD4 T Cells Support Persistent HIV-1 Transcription in Treated Aviremic Individuals.

A recent study conducted in blood has proposed CD32 as the marker identifying the "elusive" HIV reservoir. We have investigated the distribution of CD32 <sup>+</sup> CD4 T cells in blood and lymph nodes (LNs) of HIV-1-uninfected subjects and viremic untreated and long-term-treated HIV-1-infected individuals and their relationship with PD-1 <sup>+</sup> CD4 T cells. The frequency of CD32 <sup>+</sup> CD4 T cells was increased in viremic compared to treated individuals in LNs, and a large proportion (up to 50%) of CD32 <sup>+</sup> cells coexpressed PD-1 and were enriched within T follicular helper (Tfh) cells. We next investigated the role of LN CD32 <sup>+</sup> CD4 T cells in the HIV reservoir. Total HIV DNA was enriched in CD32 <sup>+</sup> and PD-1 <sup>+</sup> CD4 T cells compared to CD32 <sup>-</sup> and PD-1 <sup>-</sup> cells in both viremic and treated individuals, but there was no difference between CD32 <sup>+</sup> and PD-1 <sup>+</sup> cells. There was no enrichment of latently infected cells with inducible HIV-1 in CD32 <sup>+</sup> versus PD-1 <sup>+</sup> cells in antiretroviral therapy (ART)-treated individuals. HIV-1 transcription was then analyzed in LN memory CD4 T cell populations sorted on the basis of CD32 and PD-1 expression. CD32 <sup>+</sup> PD-1 <sup>+</sup> CD4 T cells were significantly enriched in cell-associated HIV RNA compared to CD32 <sup>-</sup> PD-1 <sup>-</sup> (averages of 5.2-fold in treated individuals and 86.6-fold in viremics), CD32 <sup>+</sup> PD-1 <sup>-</sup> (2.2-fold in treated individuals and 4.3-fold in viremics), and CD32 <sup>-</sup> PD-1 <sup>+</sup> (2.2-fold in ART-treated individuals and 4.6-fold in viremics) cell populations. Similar levels of HIV-1 transcription were found in CD32 <sup>+</sup> PD-1 <sup>-</sup> and CD32 <sup>-</sup> PD-1 <sup>+</sup> CD4 T cells. Interestingly, the proportion of CD32 <sup>+</sup> and PD-1 <sup>+</sup> CD4 T cells negatively correlated with CD4 T cell counts and length of therapy. Therefore, the expression of CD32 identifies, independently of PD-1, a CD4 T cell population with persistent HIV-1 transcription and coexpression of CD32 and PD-1, the CD4 T cell population with the highest levels of HIV-1 transcription in both viremic and treated individuals.IMPORTANCE The existence of long-lived latently infected resting memory CD4 T cells represents a major obstacle to the eradication of HIV infection. Identifying cell markers defining latently infected cells containing replication-competent virus is important in order to determine the mechanisms of HIV persistence and to develop novel therapeutic strategies to cure HIV infection. We provide evidence that PD-1 and CD32 may have a complementary role in better defining CD4 T cell populations infected with HIV-1. Furthermore, CD4 T cells coexpressing CD32 and PD-1 identify a CD4 T cell population with high levels of persistent HIV-1 transcription

Detection of Pionium with DIRAC

The aim of the DIRAC experiment at CERN is to provide an accurate determination of S-wave pion-pion scattering lengths from the measurement of the lifetime of the pi+ pi- atom. The measurement will be done with precision comparable to the level of accuracy of theoretical predictions, formulated in the context of Chiral Perturbation Theory. Therefore, the understanding of chiral symmetry breaking of QCD will be submitted to a stringent test

Lymph node migratory dendritic cells modulate HIV-1 transcription through PD-1 engagement.

T-follicular helper (Tfh) cells, co-expressing PD-1 and TIGIT, serve as a major cell reservoir for HIV-1 and are responsible for active and persistent HIV-1 transcription after prolonged antiretroviral therapy (ART). However, the precise mechanisms regulating HIV-1 transcription in lymph nodes (LNs) remain unclear. In the present study, we investigated the potential role of immune checkpoint (IC)/IC-Ligand (IC-L) interactions on HIV-1 transcription in LN-microenvironment. We show that PD-L1 (PD-1-ligand) and CD155 (TIGIT-ligand) are predominantly co-expressed on LN migratory (CD1chighCCR7+CD127+) dendritic cells (DCs), that locate predominantly in extra-follicular areas in ART treated individuals. We demonstrate that TCR-mediated HIV production is suppressed in vitro in the presence of recombinant PD-L1 or CD155 and, more importantly, when LN migratory DCs are co-cultured with PD-1+/Tfh cells. These results indicate that LN migratory DCs expressing IC-Ls may more efficiently restrict HIV-1 transcription in the extra-follicular areas and explain the persistence of HIV transcription in PD-1+/Tfh cells after prolonged ART within germinal centers

DIRAC: A High Resolution Spectrometer for Pionium Detection

The DIRAC spectrometer has been commissioned at CERN with the aim of detecting $\pi^+ \pi^-$ atoms produced by a 24 GeV/$c$ high intensity proton beam in thin foil targets. A challenging apparatus is required to cope with the high interaction rates involved, the triggering of pion pairs with very low relative momentum, and the measurement of the latter with resolution around 0.6 MeV/$c$. The general characteristics of the apparatus are explained and each part is described in some detail. The main features of the trigger system, data-acquisition, monitoring and setup performances are also given.Comment: 49 pages, 37 figures. Figures 1, 2, 5 and 28 are removed because of size limitations imposed by hep-ex. They don't offer essential information. Latex class file 'elsart.cls' also provide

Meiotic and developmental competence of prepubertal and adult swine oocytes

International audienc

Sécrétion d'oestrogènes par l'embryon porcin avant implantation

National audienc